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Modulatory effect of interleukin-1β on rat isolated basilar artery contraction
European Journal of Pharmacology 531 (2006) 238 – 245 www.elsevier.com/locate/ejphar
Modulatory effect of interleukin-1β on rat isolated basilar artery contraction Sai Wang Seto a , Yiu Wa Kwan a,⁎, Sai Ming Ngai b a
Room 409B, Basic Medical Sciences Building, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, PR China b Department of Biology, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China Received 16 June 2005; received in revised form 16 December 2005; accepted 19 December 2005 Available online 24 January 2006
Abstract An increased level of cytokine interleukin-1 (IL-1) has been detected around the site of stroke. However, the effect of IL-1β on the basilar artery has received little attention. We evaluated the effects of IL-1β on the contractile response of rat isolated basilar artery by measuring isometric tension change. IL-1β (10 ng/ml) and phenylephrine (0.1 nM) markedly enhanced U46619 (30 and 100 nM)-induced basilar artery contraction. The IL-1β-mediated potentiation was partly suppressed by zinc protoporphyrin (3 μM) and was abolished by tetrodotoxin (TTX, 100 nM), (−)-perillic acid (1 μM), PD98059 (0.3 μM), SB203580 (1 μM) and prazosin (1 μM). Our data suggest that IL-1β (10 ng/ml) causes an enhancement of U46619-mediated basilar artery contraction that probably involves TTX-sensitive neuronal release of an α1-adrenoceptor agonist and activation of p42/p44 and p38 mitogen-activated protein kinases/p21ras pathways. © 2006 Elsevier B.V. All rights reserved. Keywords: Interleukin; MAP kinase; Adrenergic agonist; Vasoconstriction
1. Introduction Stroke is an irreversible neurological deficit caused by an inadequate perfusion of a region of the brain. Occlusion of a blood vessel in the brain results in a restricted area of deep infraction (Morgan and Humphrines, 2005). Hypertension is a major risk factor for stroke and there is increasing evidence that hypertension is linked to other cardiovascular diseases, with an important feature being the development of an inflammatory response (Blake and Ridker, 2002; Virids and Schiffrin, 2003). Cytokines are a group of polypeptides or glycoproteins strongly associated with the inflammatory response (Rothwell, 1999) and have an important role in vascular injury caused by inflammation. Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines and is suggested to be involved in various cardiovascular diseases (Rothwell et al., 1997; Von der Thusen et al., 2003) including stroke. The IL-1 family comprises four proteins (IL-1α, IL-1β, IL-1Ra and Interferon-γ) that share considerable sequence homology (Dinarello, 1997). Among ⁎ Corresponding author. Tel.: +852 2609 6884; fax: +852 2603 5139. E-mail address: [email protected] (Y.W. Kwan). 0014-2999/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2005.12.038
these proteins, IL-1β is the major IL-1 cytokine found in the brain in response to systemic or local insults (Hopkins and Rothwell, 1995; Rothwell and Luheshi, 1994). It has been demonstrated that, in rodents, the expression of IL-1β protein is elevated within 1 h of experimental-induced cerebral ischaemia, leading to neuronal death (Yabuuchi et al., 1994). Cytokines, including IL-1β, can induce the expression of genes that are important for the synthesis of cytokines and other vasoactive mediators (e.g. leukotrienes, nitric oxide, bradykinin and reactive oxygen species) (Vila and Salaices, 2004). It has been reported that cytokines exert effects after both short-term exposure (1 h) (Vicaut et al., 1996) and long-term exposure (48 h) (White et al., 2000). White et al. (2000) demonstrated that, in human temporal artery, the contractile response elicited by endothelin ETB receptor activation was enhanced after a 48-h incubation with a combination of Tumor Necrosis Factor-α (TNF-α) (50 ng/ml) and IL-1 (10 ng/ml). IL-1 (20 ng/ml, 1 h incubation) enhanced angiotensin II-induced vasoconstriction of rat isolated aorta via the prostaglandin H2/thromboxane A2 cascade (Vicaut et al., 1996). In addition, IL-1 (20 ng/ml, ∼200 min incubation) inhibited phenylephrine-induced contraction of rat aortic rings by influencing protein synthesis (Beasley et al., 1989) and activating ATP-sensitive K+ channels
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(Takizawa et al., 1998). It is important to point out that IL-1 produces various responses in different vascular beds of rabbit (Robert et al., 1993). For instance, IL-1 (100 U/ml, 18 h incubation) decreased noradrenaline-induced contraction of isolated aorta, carotid artery, pulmonary artery and renal artery whereas an enhanced contraction was observed in femoral artery. However, no apparent effect of IL-1 was observed in hepatic and mesenteric arteries (Robert et al., 1993). In the brain, it has been suggested that IL-1 initiates its effect by binding to a single 80-kDa cell-surface receptor which is associated with a series of accessory proteins. These proteins are involved in nuclear transcription via nuclear factor κB and mitogen-activated protein kinase (MAPK) pathways (Eder, 1997). In rat cardiac myocytes, IL-1β induced inducible nitric oxide synthase expression and regulated the expression of cyclo-oxygenase-2 via p42/p44 and p38 MAPK pathways (LaPointe and Isenovic, 1999). Thromboxane A2 (TxA2) is a potent pro-aggregatory agent and vasoconstrictor produced from arachidonic acid metabolism via activation of the cyclo-oxygenase cascade (Narumiya et al., 1999). It has been shown that TxA 2 -induced vasoconstriction involves activation of different kinases, including protein kinase C (Murtha et al., 1999), p42/p44 MAPK (Gao et al., 2001) and p38 MAPK (Saklatvala et al., 1996). The possible roles of TxA2 release in pathophysiological conditions have been suggested to be related to enhanced production of TxA2 in coronary artery disease (Noll and Luscher, 1998), hypertension (Matrougui et al., 1997) and stroke (Touzani et al., 1999). In addition to TxA2, 5hydroxytryptamine (5-HT) is another potent vasoconstrictor of cerebral blood vessels, and 5-HT is implicated in various pathophysiological conditions including migraine (Friberg et al., 1991) and cerebral ischaemia (Feldman et al., 1997; Salomone et al., 1997) with the participation of both tyrosine kinase and protein kinase C (Kitazono et al., 1998; Murray et al., 1992; Watts et al., 1996). Despite the fact that IL-1β is possibly involved in cerebral vascular diseases, the modulatory effect of IL-1β on the basilar artery response to TxA2 and 5-HT challenge has received little attention. In this study, we investigated the vascular effect of IL-1β (10 ng/ml) on agonist (5-HT and U46619)-mediated and depolarization (high [K+]o)-induced vasoconstriction of rat isolated basilar artery and the underlying mechanism(s) involved. 2. Materials and methods 2.1. Animals Rats (Sprague–Dawley, male, 300–350 g) were housed under a 12 : 12-h light–dark cycle (7:00 a.m. ON; 7:00 p.m. OFF) and were given standard rat chow and water ad libitum before they were used for our experiments. The Animal Experimentation Ethics Committee of The Chinese University of Hong Kong (Hong Kong SAR, PR of China) approved the experiments performed in this study (approval ref. no: 00/017/ MIS). The recommendations from the Declaration of Helsinki
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and the internationally accepted principles for the use of experimental animals were adhered to. Every effort was made to limit animal suffering and to limit the number of animals used in these experiments. 2.2. Tissue preparation Animals were anaesthetized in an air-tight box with CO2 overdose and killed by cervical dislocation. The brain was immediately removed and the basilar artery (length: ∼0.7 cm; O.D. ∼200–250 μm) was isolated. Fat and connective tissue were carefully removed under a dissecting microscope. Care was taken not to touch the lumen of the basilar artery during dissection, to ensure that the endothelium was intact. Four arterial rings (1 mm in length) were obtained from each basilar artery preparation and only one ring was used for each drug treatment. 2.3. In vitro isometric tension measurement The arterial ring was mounted in a 5-ml wire myograph containing Krebs' solution (gassed with 16% O2/6% CO2 balanced with N2; pH = 7.4; 37 ± 1 °C; pO2 ∼ 100 mm Hg) of the following composition (mM): NaCl 118, KCl 4.7, MgSO4 1.2, KH2PO4 1.2, NaHCO3 25, glucose 11 and CaCl2 1.8. In some preparations, the endothelium was carefully removed by rubbing the intima of the artery with a human hair. Endothelium removal was confirmed by the failure of acetylcholine (10 μM)induced relaxation. Isometric tension change was measured by using Myodaq (version 2.01 program) (National Instrument Cooperation, U.S.A.). Preparations were equilibrated under a resting tension of 3.0 ± 0.3 mN in the bath solution for ∼30 min. Resting tension was readjusted, if necessary, before the experiments were started. Under resting tension, two concentration–response curves were constructed for each preparation, with the first curve serving as control. Cumulative concentrations of high [K+]o (10–40 mM), 5-hydroxytryptamine (5-HT) (1 nM–3 μM) or thromboxane A2 mimetic U46619 (0.1–100 nM) were added to obtain the first concentration–response curve. A 90-min resting period, with regular washes using drug-free Krebs' solution, was allowed before the construction of the second concentration–response curve for an agonist. In the preliminary study, the first concentration–response curve for an individual contractile agent (n = 5–6) overlapped with the second curve, indicating the reproducibility of the contractile response recorded. The modulatory effect of interleukin IL-1β was determined by incubating the arterial preparation with IL-1β (10 ng/ml) for 90 min before the construction of the second curve (in the continuous presence of IL-1β) for the contractile agent. Various blockers were incubated with basilar artery preparations for 30 min before the application of IL-1β (10 ng/ml). Where stated, the concentration of inhibitors used in this study was the reported effective concentration of the individual agent, based on our previous studies with different vascular smooth muscle preparations (Au et al., 2003; Choy et al., 2002; Kwan et al., 1999).
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2.4. Chemicals Physiological salts (GR grade) for preparing Krebs' solution for isometric tension measurement were obtained from Merck (Darmstadt, Germany). Interleukin-1β (human, recombinant) was purchased from PeproTech (U.K.). 5-Hydroxytryptamine hydrochloride, acetylcholine hydrochloride, L-phenylephrine hydrochloride, indomethacin, cyclohexamide and zinc protoporphyrin were obtained from Sigma-Aldrich Chemicals Co. (U.S.A.). Prazosin hydrochloride and yohimbine hydrochloride were purchased from Tocris (U.K.). 9,11-Dideoxy-9α,11αmethanoepoxy-prostaglandin F2α (U46619), 2′-amino-3′methoxyflavone (PD98059), (−)-perillic acid, tetrodotoxin
and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) were obtained from Calbiochem-Novabiochem. Incorp. (U.S.A.). 2.5. Statistical analysis Data are expressed as means ± S.E.M.; n refers to the number of rats from which the basilar artery was taken for isometric tension measurements. Statistical analysis of raw data (i.e. tension developed in millinewton) was performed using Student's paired (two-way) t-test and analysis of variance (ANOVA), where appropriate. Differences were considered to be statistically significant at a value of P b 0.05.
Fig. 1. (A) Typical recordings of U46619-induced contraction of isolated basilar artery (endothelium intact) from Sprague–Dawley rats in the absence and the presence of interleukin IL-1β (10 ng/ml, 90-min incubation). Calibration bars: 2 mN and 10 min. (B) A comparison of U46619 (30 and 100 nM)-induced contraction (in mN) recorded with (close symbols: ●, ♦) (n = 6) and without (open symbols: ○, ⋄) (n = 6) IL-1β (10 ng/ml, 90-min incubation). (C) For illustration, cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, n = 6) IL-1β (10 ng/ml, 90-min incubation) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats are presented. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control.
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3. Results Under resting tension, cumulative application of IL-1β (0.1 to 30 ng/ml) and phenylephrine (0.1 nM to 100 μM) did not alter the basal tone of isolated basilar artery (endothelium intact, n = 6; endothelium denuded, n = 6) (data not shown). However, U46619 (10–100 nM), high [K+]o (10–40 mM) (EC50 = 27.33 mM; Emax = 4.35 ± 2.05 mN) and 5-hydroxytryptamine (5-HT, 1 nM–3 μM) (EC50 = 0.1 μM; Emax = 7.54 ± 1.63 mN) elicited a concentration-dependent contraction of isolated basilar artery (endothelium intact, under resting tension) (data not shown). IL-1β (10 ng/ml, 90-min incubation) moderately potentiated the U46619 (30 and 100 nM)-elicited basilar artery (endothelium intact) contraction (n = 6) (P b 0.05 compared to control) (Fig. 1A). An approximately 0.5 log unit leftward shift (Fig. 1B) with an increased (∼50%) maximum contraction (at 100 nM) of the concentration–response curve for U46619 was observed (Fig. 1C). The IL-1β (10 ng/ml)-mediated potentiation persisted after endothelium denudation (n = 4) (data not shown). In contrast, IL-1β (10 ng/ml) failed to alter the high [K+]o(EC 50 = 29.33 mM; E max = 4.08 ± 1.36 mN) and 5-HT-
Fig. 2. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus tetrodotoxin (100 nM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration–response curves for the effect of U46619 (0.1– 100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus zinc protoporphyrin (3 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
Fig. 3. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) (○, n = 6) (control), and in the presence of IL-1β (10 ng/ml) (●, n = 6), phenylephrine (0.1 nM) (⋄, n = 6), IL-1β (10 ng/ml) plus prazosin (1 μM) (▴, n = 6) and phenylephrine (0.1 nM) plus prazosin (1 μM) (O, n = 6) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration– response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus yohimbine (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
(EC50 = 0.1 μM; Emax = 7.08 ± 1.37 mN) elicited basilar artery contraction (endothelium intact). Application of tetrodotoxin (TTX) (100 nM) (n = 6) (Fig. 2A) eradicated, whereas zinc protoporphyrin (ZnPP) (3 μM, n = 6) (Fig. 2B) partly reduced, the IL-1β-mediated potentiation effect. A higher concentration of ZnPP (10 μM) was also tested but it markedly suppressed the U46619-elicited contraction (n = 5) (data not shown). Prazosin (1 μM, an α1adrenoceptor blocker, n = 6) (Fig. 3A), but not yohimbine (1 μM, an α2-adrenoceptor blocker, n = 6) (Fig. 3B), eradicated the IL-1β-mediated potentiation of the U46619-elicited basilar artery (endothelium intact) contraction. Tetrodotoxin (n = 6), prazosin (n = 6) or yohimbine (n = 6), applied alone, did not modify the U46619-induced basilar artery contraction (data not shown). Phenylephrine (0.1 nM), applied alone, caused potentiation of the U46619-elicited basilar artery (endothelium intact) contraction (n = 6) (Fig. 3A). Higher concentrations of phenylephrine (1 nM, n = 5; 10 nM, n = 5) caused no further enhancement (compared to 0.1 nM phenylephrine) of the U46619-mediated basilar artery contraction (data not shown). In addition, the phenylephrine (0.1 nM)-mediated potentiation
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of the U46619-elicited basilar artery contraction was sensitive to prazosin (1 μM, n = 6) (Fig. 3A). Administration of PD98059 (0.3 μM) (Fig. 4A), (−)-perillic acid (1 μM) (Fig. 4B) and SB203580 (1 μM) (Fig. 4C) inhibited the IL-1β-mediated potentiation of the contraction. PD98059 (0.3 μM) (n = 6), SB203580 (1 μM) (n = 6) or
(−)-perillic acid (1 μM) (n = 6), applied alone, did not alter the basal resting tension and the U46619-induced basilar artery (endothelium intact) contraction. In contrast, cyclohexamide (1 μM) (n = 5) (data not shown) and indomethacin (1 μM) (n = 5) (data not shown) had no apparent effect on the IL-1β-mediated potentiation of the U46619-induced contraction of basilar artery (endothelium intact). Indomethacin or cyclohexamide, applied alone, did not alter the U46619-induced basilar artery contraction (in both endothelium intact and denuded preparations) (n = 5–6) or the resting tension of basilar artery (n = 5–6) (data not shown). 4. Discussion
Fig. 4. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus PD98059 (0.3 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus (−)-perillic acid (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (C) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL1β (10 ng/ml) plus SB203580 (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
The major findings of this study demonstrate that a thromboxane A2 mimetic (U46619), 5-hydroxytryptamine (5-HT) and high [K+ ]o but not phenylephrine (an α1adrenoceptor agonist), elicit a concentration-dependent contraction of rat isolated basilar artery under resting tension, as observed in vivo (Fujii et al., 1990). Our results are consistent with those of previous studies (Houston and Vanhoutte, 1986; Uddman et al., 1999) in which the release of both thromboxane A2 and 5-HT was found to be important in physiological and pathophysiological conditions affecting the cerebral circulation (Satoh et al., 1991). In contrast to previous studies (Boulanger et al., 1994; Tsang et al., 2004), phenylephrine (10 nM to 100 μM) failed to cause contraction of the rat isolated basilar artery. This may be due to the use of “different gas mixtures” and the difference of pO2 measured in the organ bath. In our study, we used a gas mixture of 16% O2/6% CO2 (balanced with N2) (MacLean et al., 1996; Au et al., 2003), which provided a physiological pO2 ∼ 100 mm Hg (Takada et al., 2001) in the organ bath. However, in the other study in which phenylephrine caused basilar artery contraction in vitro (Tsang et al., 2004), experiments were performed under non-physiological hyperoxic conditions (i.e. a gas mixture of 95% O2/5% CO2, pO2 N 500 mm Hg) (Kwan et al., 1989). The basilar artery is highly sensitive to pO2 in vitro and in vivo. In our study, incubation for 90 min with IL-1β (10 ng/ml, a level that can be detected during cerebral ischaemia/stroke) (Legos et al., 2000) significantly enhanced the U46619-elicited basilar artery contraction. More importantly, zinc protoporphyrin (ZnPP) (3 μM, a putative IL-1 receptor antagonist) (Yamasaki et al., 1995) suppressed, but did not abolish, the IL-1β-mediated potentiation of the U46619-induced basilar artery contraction. A higher concentration of ZnPP (10 μM) resulted in a marked suppression of the U46619-induced contraction, suggesting that ZnPP may have another effect (such as activation of guanylase cyclase), as reported previously (Luo and Vincent, 1994). Nevertheless, our results suggest that activation of IL-1 receptors may probably be involved in the IL1β-mediated potentiation of the basilar artery contraction elicited by U46619. In anaesthetized dogs (Osuka et al., 1997), intra-cisternal administration of interleukin IL-1β (0.03 and 0.3 μg) dilated the basilar artery in a dose-dependent, ZnPP (30 μg)-sensitive manner. However, in our study with rat isolated basilar artery,
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application of IL-1β (1–30 ng/ml, 90-min incubation) did not alter the basal tone of the preparations. The underlying mechanism responsible for the discrepancy is not known, but it may be related to the species and the concentration/dose of IL1β used in these studies. The presence of functional endothelium is not important because mechanical removal of the endothelium did not modify the IL-1β (1–30 ng/ml, 90-min incubation)-mediated effect, and no apparent change in basal tone of basilar artery was observed. Interestingly, the IL-1β-mediated potentiation of basilar artery contraction was “selective” as neither high [K+]o- nor 5-HT-induced basilar artery contraction was affected by incubation with IL-1β. The underlying mechanism responsible for the differential enhancement by IL-1β of basilar artery contraction is not known. It may be related to different cellular signalling mechanisms involved in high [K+]o- and 5HT-induced vasoconstriction (Tasaki et al., 2003). In most previous studies (Pickker et al., 2002; Takizawa et al., 1998; Touzani et al., 1999), application of IL-1β generally resulted in a suppression, rather than a potentiation, of the contractile response of different blood vessels. Our novel results, for the first time, indicate that incubation with IL-1β resulted in an enhancement of U46619-elicited basilar artery contraction, which may be important in the development of stroke. It is well documented that cerebral arteries of different species are highly innervated (Bunc et al., 2001; El-Assouad and Tayebati, 2002; Handa et al., 1993; Tsai et al., 1989), and that neurotransmitters released from nerve terminals are important for maintaining the vasomotor tone of the cerebral circulation. In order to delineate the underlying mechanisms involved in the IL-1β-mediated potentiation of the U46619induced basilar artery contraction, we considered the possible release of neurotransmitter(s) from nerve terminals. The presence of tetrodotoxin (100 nM, a neuronal Na+ channel blocker) eradicated the IL-1β-mediated potentiation of the response, suggesting that the neuronal release of substance(s) from nerve terminals upon the application of IL-1β probably plays an obligatory role. As in vas deferens preparations (Trachte, 1986), the chemical (s) released from neurons following IL-1β application were identified by using different pharmacological tools. Prazosin (1 μM, an α1-adrenoceptor antagonist), but not yohimbine (1 μM, an α2-adrenoceptor antagonist), abolished the IL-1βmediated potentiation. Phenylephrine (0.1 nM, an α1-adrenoceptor agonist) applied alone mimicked the potentiation by IL1β, and the enhancement of the U46619-induced contraction observed was prevented by prazosin. It is important to appreciate that neuronally released α1-adrenoceptor agonist and exogenous phenylephrine only play a modulatory role, rather than exert a “direct vascular effect”, on rat basilar artery: phenylephrine (0.1, 1, 10, 30 and 100 nM) and IL-1β (10 ng/ml), applied alone, did not alter the basal tone of rat isolated basilar artery. Taken together, our results suggest that IL-1β (10 ng/ml) causes the release of a substance from nerve terminals that acts on α1adrenoceptors and subsequently causes an enhancement of U46619-induced basilar artery contraction.
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In addition to the well-documented role in cellular proliferation (Lin et al., 2005), the mitogen-activated protein kinase (MAPK) cascade has been suggested to have an important role in vascular smooth muscle contraction (Tasaki et al., 2003; Tsai and Jiang, 2005). In hypothalamic corticotropin-releasing neurons, IL-1β (0.25 μg/kg) induced a long-lasting increase in noradrenaline release (Schmidt et al., 2001). In rat hippocampal slices, IL-1β (3 × 10− 18–3 × 10− 14 M) triggered transportermediated [3 H]-purine efflux in a concentration-dependent manner via glutamate receptor-mediated excitatory synaptic transmission and activation of p38 MAPK (Sperlagh et al., 2004). The neuronal release of mediator(s) elicited by IL-1β in the basilar artery may involve the MAPK pathway. To explore the possible involvement of the MAPK cascade, the effect of PD98059 (a p42/44 MAPK inhibitor), (−)-perillic acid (a p21ras inhibitor) and SB203580 (a p38 MAPK inhibitor) was examined. In rat isolated basilar artery, incubation with these inhibitors, individually, attenuated the IL-1β-mediated potentiation of the U46619-elicited contraction. In contrast, it has been reported that the p38 MAPK pathway is not involved in the U46619-induced contraction of rat thoracic aorta (Tasaki et al., 2003). However, in our study, the U46619-induced contraction enhanced by IL-1β was sensitive to p38 MAPK inhibition. Taken together, our results demonstrate that the IL1β-mediated potentiation of the U46619-elicited contraction probably involves the p42/p44 and p38 MAPKs/p21 ras signalling cascade. In our study, the basilar artery was incubated with IL-1β (10 ng/ml) for 90 min before the second challenge with U46619. The possibility that protein synthesis may be responsible for the IL-1β-induced response was also considered. However, cyclohexamide (1 μM, a protein synthesis inhibitor) did not modify the IL-1β-induced response, implying that the potentiation effect probably relies on preformed substance(s) present inside the nerve terminal of the basilar artery rather than on IL-1β-induced synthesis of mediators during the incubation period. However, in anaesthetized dogs, intra-cisternal application of IL-1β caused an increase in eicosanoid concentration (Tasaki et al., 2003). Our results argue for the participation of cyclo-oxygenase cascade/ eicosanoid generation because indomethacin (1 μM, a nonselective cyclo-oxygenase inhibitor) failed to alter the IL-1βmediated potentiation of the U46619-elicited basilar artery contraction. In conclusion, our novel data demonstrate, for the first time, that IL-1β causes a selective enhancement of U46619-mediated rat basilar artery contraction, an effect that is probably mediated by the neuronal release of an α1-adrenoceptor agonist and activation of p42/p44 and p38 MAPK/p21ras pathways. Acknowledgements Mr. S.W. Seto is a recipient of a post-graduate (Ph.D.) studentship of the Department of Pharmacology (The Chinese University of Hong Kong, Hong Kong SAR, PR China). This project is supported by the RGC Earmarked Grant of Hong Kong SAR, PR China (Ref.: 4166/02M).
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References Au, A.L.S., Kwan, Y.W., Kwok, C.C., Zhang, R.Z., He, G.W., 2003. Mechanisms responsible for the in vitro relaxation of ligustrazine on porcine left anterior descending coronary artery. Eur. J. Pharmacol. 468, 199–207. Beasley, D., Cohen, R.A., Levinsky, N.G., 1989. Interleukin 1 inhibits contraction of vascular smooth muscle. J. Clin. Invest. 83, 331–335. Blake, G.J., Ridker, P.M., 2002. Inflammatory bio-markers and cardiovascular risk prediction. J. Intern. Med. 242, 283–294. Boulanger, C.M., Nakashima, M., Olmos, L., Joly, G., Vanhoutte, P.M., 1994. Effects of the Ca2+ antagonist RO 40-5967 on endotheliumdependent responses of isolated arteries. J. Cardiovasc. Pharmacol. 23, 869–876. Bunc, G., Kovacic, S., Strnad, S., 2001. Evaluation of functional response of cerebral arteries by a new morphometric technique. Auto. Neurosci. 93, 41–47. Choy, W.Y., Wong, Y.F., Kwan, Y.W., Au, A.L.S., Lau, W.H., Raymond, K., Zuo, J.Z., 2002. Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery. Eur. J. Pharmacol. 434, 55–64. Dinarello, C.A., 1997. Interleukin-1. Cytokine Growth Factor Rev. 8, 253–265. Eder, J., 1997. Tumour necrosis factor alpha and interleukin 1 signalling: do MAPKK kinases connect it all? TiPS 18, 319–322. El-Assouad, D., Tayebati, S.K., 2002. Cholinergic innervation of pial arteries in senescent rats: an immunohistochemical study. Mech. Ageing Dev. 123, 529–536. Feldman, S.R., Meyer, J.S., Quenzer, L.F., 1997. Principles of Neuropsychopharmacology. Sinauer Associates Inc., Publishers. Friberg, L., Olesen, J., Iversen, H.K., Sperling, B., 1991. Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet 338, 13–17. Fujii, K., Heistad, D.D., Faraci, F.M., 1990. Vasomotion of basilar arteries in vivo. Am. J. Physiol. 258, H1829–H1834. Gao, Y., Tang, S., Zhou, S., Ware, J.A., 2001. The thromboxane A2 receptor activates mitogen-activated protein kinase via protein kinase C-dependent Gi coupling and Src-dependent phosphorylation of the epidermal growth factor receptor. J. Pharmacol. Exp. Ther. 296, 426–433. Handa, Y., Nojyo, Y., Tamamaki, N., Tsuchida, A., Kubota, T., 1993. Development of the sympathetic innervation to the cerebral arterial system in neonatal rats as revealed by anterograde labelling with wheat germ agglutinin-horseradish peroxidase. Exp. Brain Res. 94, 216–224. Hopkins, S.J., Rothwell, N.J., 1995. Cytokines in the nervous system I: expression and recognition. TiNS 18, 83–88. Houston, D.S., Vanhoutte, P.M., 1986. Serotonin and the vascular system. Role in health and disease, and implications for therapy. Drugs 31, 149–163. Kitazono, T., Ibayashi, S., Nagao, T., Kagiyama, T., Kitayama, J., Fujishima, M., 1998. Role of tyrosine kinase in serotonin-induced constriction of the basilar artery in vivo. Stroke 29, 494–497. Kwan, Y.W., Wadsworth, R.M., Kane, K.A., 1989. Effects of hypoxia on the pharmacological responsiveness of isolated coronary artery rings from the sheep. Br. J. Pharmacol. 96, 849–856. Kwan, Y.W., To, K.W., Lau, W.M., Tsang, S.H., 1999. Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar– Kyoto rats. Eur. J. Pharmacol. 365, 241–251. LaPointe, M.C., Isenovic, E., 1999. Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p38 MAPK signalling pathways in cardiac myocytes. Hypertension 33, 276–282. Legos, J.J., Whitmore, R.G., Erhardt, J.A., Parsons, A.A., Tuma, R.F., Barone, F.C., 2000. Quantitative changes in interleukin proteins following focal stroke in the rat. Neurosci. Lett. 282, 189–192. Lin, X., Ramamurthy, S.K., Le Breton, G.C., 2005. Thromboxane a receptormediated cell proliferation, survival and gene expression in oligodendrocytes. J. Neurochem. 93, 257–268. Luo, D., Vincent, S.R., 1994. Metalloporphyrins inhibits nitric oxide dependent cGMP formation in vivo. Eur. J. Pharmacol. 267, 263–267.
MacLean, M.R., Sweeney, G., Baird, M., McCulloch, K.M., Houslay, M., Morecroft, I., 1996. 5-Hydroxytryptamine receptors mediated vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats. Br. J. Pharmacol. 119, 917–930. Matrougui, K., Maclouf, J., Levy, B.I., Henrion, D., 1997. Impaired nitric oxideand prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats. Hypertension 30, 942–947. Morgan, L., Humphrines, S.E., 2005. The genetic of stroke. Curr. Opin. Lipidol. 16, 193–199. Murray, M.A., Faraci, F.M., Heistad, D.D., 1992. Role of protein kinase C in constrictor responses of the rat basilar artery in vivo. J. Physiol. 445, 169–179. Murtha, Y.M., Allen, B.M., James, A.O., 1999. The role of protein kinase C in thromboxane A2-induced pulmonary artery vasoconstriction. J. Biomed. Sci. 6, 293–295. Narumiya, S., Sugimoto, Y., Ushikubi, F., 1999. Prostanoid receptors: structures, properties, and functions. Physiol. Rev. 79, 1193–1226. Noll, G., Luscher, T.F., 1998. The endothelium in acute coronary syndromes. Eur. Heart J. 19, C30–C38. Osuka, K., Suzuki, Y., Watanabe, Y., Dogan, A., Takayasu, M., Shibuya, M., Yoshida, J., 1997. Vasodilator effects on canine basilar artery induced by intracisternal interleukin-1 beta. J. Cereb. Blood Flow Metab. 17, 1337–1345. Pickker, P., Netea, M.G., Van der Meer, J.W.M., Smits, P., 2002. TNF and IL-1 exert no direct vasoactivity in human isolated resistance arteries. Cytokine 20, 244–246. Robert, R., Chapelain, B., Neliat, G., 1993. Different effects of IL-1 on reactivity of arterial vessels isolated from various vascular beds in the rabbit. Circ. Shock 40, 139–143. Rothwell, N.J., 1999. Cytokines — killers in the brain? J. Physiol. 514, 3–17. Rothwell, H.J., Luheshi, G.N., 1994. Pharmacology of interleukin-1 actions in the brain. Adv. Pharmacol. 25, 1–20. Rothwell, N.J., Loddick, S.A., Stroemer, P., 1997. Interleukins and cerebral ischaemia. Int. Rev. Neurobiol. 40, 281–298. Saklatvala, J., Rawlinson, L., Waller, R.J., Sarsfield, S., Lee, J.C., Barnes, M.J., Farndale, R.W., 1996. Role of p38 mitogen-activated protein kinase caused by collagen or a thromboxane analogue. J. Biol. Chem. 271, 6586–6589. Salomone, S., Morel, N., Godfraind, T., 1997. Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats. Br. J. Pharmacol. 121, 1051–1058. Satoh, S., Suzuki, Y., Harada, T., Ikegaki, I., Asano, T., Shibuya, M., Sugita, K., Saito, A., 1991. The role of platelets in the development of cerebral vasospasm. Brain Res. Bull. 27, 663–668. Schmidt, E.D., Schoffelmeer, A.N.M., De Vries, T.J., Wardeh, G., Dogterom, G., Bol, J.G., Binnekade, R., Tilders, F.J., 2001. A single administration of interleukin-1 or amphetamine induces long-lasting increases in evoked noradrenaline release in the hypothalamus and sensitization of ACTH and corticosterone responses in rats. Eur. J. Neurosci. 13, 1923–1930. Sperlagh, B., Baranyi, M., Hasko, G., Vizi, S.E., 2004. Potent effect of interleukin-1β (to evoke ATP and adenosine release from rat hippocampal slices. J. Neuroimmunol. 151, 33–39. Takada, J., Ibayashi, S., Nagao, T., Ooboshi, H., Kitazono, T., Fujishima, M., 2001. Bradykinin mediates the acute effect of an angiotensin-converting enzyme inhibitor on cerebral autoregulation in rats. Stroke 32, 1216–1219. Takizawa, S., Izaki, H., Karaki, H., 1998. Possible involvement of K+ channel opening to the interleukin-1 beta — induced inhibition of vascular smooth muscle contraction. J. Vet. Med. Sci. 61, 357–360. Tasaki, K., Hori, M., Ozaki, H., Karaki, H., Wakabayashi, I., 2003. Difference in signal transduction mechanisms involved in 5-hydroxytryptamine- and U46619-induced vasoconstriction. J. Smooth Muscle Res. 39, 107–117. Touzani, O., Boutin, H., Chuquent, J., Rothwell, N., 1999. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J. Neuroimmunol. 100, 203–215. Trachte, G.J., 1986. Thromboxane agonist (U46619) potentiates norepinephrine efflux from adrenergic nerves. J. Pharmacol. Exp. Ther. 237, 473–477. Tsai, M.H., Jiang, M.J., 2005. Extracellular signal-regulated kinase 1/2 in contraction of vascular smooth muscle. Life Sci. 76, 877–888.
S.W. Seto et al. / European Journal of Pharmacology 531 (2006) 238–245 Tsai, S.H., Tew, J.M., Shipley, M.T., 1989. Cerebral arterial innervation: II. Development of calcitonin-gene-related peptide and norepinephrine in the rat. J. Comp. Neurol. 279, 1–12. Tsang, S.Y., Yao, X., Essin, K., Wong, C.M., Chan, F.L., Gollasch, M., Huang, Y., 2004. Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels. Stroke 35, 1709–1714. Uddman, E., Moller, S., Adner, M., Edvinsson, L., 1999. Cytokines induce endothelin ETB receptor-mediated contraction. Eur. J. Pharmacol. 376, 223–232. Vicaut, E., Rasetti, C., Baudry, N., 1996. Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotension II in rat aorta. J. Appl. Physiol. 80, 1891–1897. Vila, E., Salaices, M., 2004. Cytokines and vascular reactivity in resistance arteries. J. Physiol. 288, H1016–H1021. Virids, A., Schiffrin, E.L., 2003. Vascular inflammation: a role in vascular disease in hypertension? Curr. Opin. Nephrol. Hypertens. 12, 181–187.
245
Von der Thusen, J.H., Kuiper, J., Van Berkel, T.J.C., Biessen, E.A.L., 2003. Interleukins in atherosclerosis: molecular pathways and therapeutic potential. Pharmacol. Rev. 55, 133–166. Watts, S.W., Yeum, C.H., Campbell, G., Webb, R.C., 1996. Serotonin stimulates protein tyrosyl phosphorylation and vascular contraction via tyrosine kinase. J. Vasc. Res. 33, 288–298. White, L.R., Juul, L., Skaanes, K.O., Aasly, J., 2000. Cytokine enhancement of endothelium ETB receptor-mediated contraction in human temporal artery. Eur. J. Pharmacol. 406, 117–122. Yabuuchi, K., Minami, M., Katsumata, S., Yamasaki, A., Satoh, M.A., 1994. An in situ hybridization study of interleukin-1 beta induced by transient forebrain ischaemia in the rat brain. Mol. Brain Res. 26, 135–142. Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., Kogure, K., 1995. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke 26, 676–681.
Modulatory effect of interleukin-1β on rat isolated basilar artery contraction Sai Wang Seto a , Yiu Wa Kwan a,⁎, Sai Ming Ngai b a
Room 409B, Basic Medical Sciences Building, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, PR China b Department of Biology, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China Received 16 June 2005; received in revised form 16 December 2005; accepted 19 December 2005 Available online 24 January 2006
Abstract An increased level of cytokine interleukin-1 (IL-1) has been detected around the site of stroke. However, the effect of IL-1β on the basilar artery has received little attention. We evaluated the effects of IL-1β on the contractile response of rat isolated basilar artery by measuring isometric tension change. IL-1β (10 ng/ml) and phenylephrine (0.1 nM) markedly enhanced U46619 (30 and 100 nM)-induced basilar artery contraction. The IL-1β-mediated potentiation was partly suppressed by zinc protoporphyrin (3 μM) and was abolished by tetrodotoxin (TTX, 100 nM), (−)-perillic acid (1 μM), PD98059 (0.3 μM), SB203580 (1 μM) and prazosin (1 μM). Our data suggest that IL-1β (10 ng/ml) causes an enhancement of U46619-mediated basilar artery contraction that probably involves TTX-sensitive neuronal release of an α1-adrenoceptor agonist and activation of p42/p44 and p38 mitogen-activated protein kinases/p21ras pathways. © 2006 Elsevier B.V. All rights reserved. Keywords: Interleukin; MAP kinase; Adrenergic agonist; Vasoconstriction
1. Introduction Stroke is an irreversible neurological deficit caused by an inadequate perfusion of a region of the brain. Occlusion of a blood vessel in the brain results in a restricted area of deep infraction (Morgan and Humphrines, 2005). Hypertension is a major risk factor for stroke and there is increasing evidence that hypertension is linked to other cardiovascular diseases, with an important feature being the development of an inflammatory response (Blake and Ridker, 2002; Virids and Schiffrin, 2003). Cytokines are a group of polypeptides or glycoproteins strongly associated with the inflammatory response (Rothwell, 1999) and have an important role in vascular injury caused by inflammation. Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines and is suggested to be involved in various cardiovascular diseases (Rothwell et al., 1997; Von der Thusen et al., 2003) including stroke. The IL-1 family comprises four proteins (IL-1α, IL-1β, IL-1Ra and Interferon-γ) that share considerable sequence homology (Dinarello, 1997). Among ⁎ Corresponding author. Tel.: +852 2609 6884; fax: +852 2603 5139. E-mail address: [email protected] (Y.W. Kwan). 0014-2999/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2005.12.038
these proteins, IL-1β is the major IL-1 cytokine found in the brain in response to systemic or local insults (Hopkins and Rothwell, 1995; Rothwell and Luheshi, 1994). It has been demonstrated that, in rodents, the expression of IL-1β protein is elevated within 1 h of experimental-induced cerebral ischaemia, leading to neuronal death (Yabuuchi et al., 1994). Cytokines, including IL-1β, can induce the expression of genes that are important for the synthesis of cytokines and other vasoactive mediators (e.g. leukotrienes, nitric oxide, bradykinin and reactive oxygen species) (Vila and Salaices, 2004). It has been reported that cytokines exert effects after both short-term exposure (1 h) (Vicaut et al., 1996) and long-term exposure (48 h) (White et al., 2000). White et al. (2000) demonstrated that, in human temporal artery, the contractile response elicited by endothelin ETB receptor activation was enhanced after a 48-h incubation with a combination of Tumor Necrosis Factor-α (TNF-α) (50 ng/ml) and IL-1 (10 ng/ml). IL-1 (20 ng/ml, 1 h incubation) enhanced angiotensin II-induced vasoconstriction of rat isolated aorta via the prostaglandin H2/thromboxane A2 cascade (Vicaut et al., 1996). In addition, IL-1 (20 ng/ml, ∼200 min incubation) inhibited phenylephrine-induced contraction of rat aortic rings by influencing protein synthesis (Beasley et al., 1989) and activating ATP-sensitive K+ channels
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(Takizawa et al., 1998). It is important to point out that IL-1 produces various responses in different vascular beds of rabbit (Robert et al., 1993). For instance, IL-1 (100 U/ml, 18 h incubation) decreased noradrenaline-induced contraction of isolated aorta, carotid artery, pulmonary artery and renal artery whereas an enhanced contraction was observed in femoral artery. However, no apparent effect of IL-1 was observed in hepatic and mesenteric arteries (Robert et al., 1993). In the brain, it has been suggested that IL-1 initiates its effect by binding to a single 80-kDa cell-surface receptor which is associated with a series of accessory proteins. These proteins are involved in nuclear transcription via nuclear factor κB and mitogen-activated protein kinase (MAPK) pathways (Eder, 1997). In rat cardiac myocytes, IL-1β induced inducible nitric oxide synthase expression and regulated the expression of cyclo-oxygenase-2 via p42/p44 and p38 MAPK pathways (LaPointe and Isenovic, 1999). Thromboxane A2 (TxA2) is a potent pro-aggregatory agent and vasoconstrictor produced from arachidonic acid metabolism via activation of the cyclo-oxygenase cascade (Narumiya et al., 1999). It has been shown that TxA 2 -induced vasoconstriction involves activation of different kinases, including protein kinase C (Murtha et al., 1999), p42/p44 MAPK (Gao et al., 2001) and p38 MAPK (Saklatvala et al., 1996). The possible roles of TxA2 release in pathophysiological conditions have been suggested to be related to enhanced production of TxA2 in coronary artery disease (Noll and Luscher, 1998), hypertension (Matrougui et al., 1997) and stroke (Touzani et al., 1999). In addition to TxA2, 5hydroxytryptamine (5-HT) is another potent vasoconstrictor of cerebral blood vessels, and 5-HT is implicated in various pathophysiological conditions including migraine (Friberg et al., 1991) and cerebral ischaemia (Feldman et al., 1997; Salomone et al., 1997) with the participation of both tyrosine kinase and protein kinase C (Kitazono et al., 1998; Murray et al., 1992; Watts et al., 1996). Despite the fact that IL-1β is possibly involved in cerebral vascular diseases, the modulatory effect of IL-1β on the basilar artery response to TxA2 and 5-HT challenge has received little attention. In this study, we investigated the vascular effect of IL-1β (10 ng/ml) on agonist (5-HT and U46619)-mediated and depolarization (high [K+]o)-induced vasoconstriction of rat isolated basilar artery and the underlying mechanism(s) involved. 2. Materials and methods 2.1. Animals Rats (Sprague–Dawley, male, 300–350 g) were housed under a 12 : 12-h light–dark cycle (7:00 a.m. ON; 7:00 p.m. OFF) and were given standard rat chow and water ad libitum before they were used for our experiments. The Animal Experimentation Ethics Committee of The Chinese University of Hong Kong (Hong Kong SAR, PR of China) approved the experiments performed in this study (approval ref. no: 00/017/ MIS). The recommendations from the Declaration of Helsinki
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and the internationally accepted principles for the use of experimental animals were adhered to. Every effort was made to limit animal suffering and to limit the number of animals used in these experiments. 2.2. Tissue preparation Animals were anaesthetized in an air-tight box with CO2 overdose and killed by cervical dislocation. The brain was immediately removed and the basilar artery (length: ∼0.7 cm; O.D. ∼200–250 μm) was isolated. Fat and connective tissue were carefully removed under a dissecting microscope. Care was taken not to touch the lumen of the basilar artery during dissection, to ensure that the endothelium was intact. Four arterial rings (1 mm in length) were obtained from each basilar artery preparation and only one ring was used for each drug treatment. 2.3. In vitro isometric tension measurement The arterial ring was mounted in a 5-ml wire myograph containing Krebs' solution (gassed with 16% O2/6% CO2 balanced with N2; pH = 7.4; 37 ± 1 °C; pO2 ∼ 100 mm Hg) of the following composition (mM): NaCl 118, KCl 4.7, MgSO4 1.2, KH2PO4 1.2, NaHCO3 25, glucose 11 and CaCl2 1.8. In some preparations, the endothelium was carefully removed by rubbing the intima of the artery with a human hair. Endothelium removal was confirmed by the failure of acetylcholine (10 μM)induced relaxation. Isometric tension change was measured by using Myodaq (version 2.01 program) (National Instrument Cooperation, U.S.A.). Preparations were equilibrated under a resting tension of 3.0 ± 0.3 mN in the bath solution for ∼30 min. Resting tension was readjusted, if necessary, before the experiments were started. Under resting tension, two concentration–response curves were constructed for each preparation, with the first curve serving as control. Cumulative concentrations of high [K+]o (10–40 mM), 5-hydroxytryptamine (5-HT) (1 nM–3 μM) or thromboxane A2 mimetic U46619 (0.1–100 nM) were added to obtain the first concentration–response curve. A 90-min resting period, with regular washes using drug-free Krebs' solution, was allowed before the construction of the second concentration–response curve for an agonist. In the preliminary study, the first concentration–response curve for an individual contractile agent (n = 5–6) overlapped with the second curve, indicating the reproducibility of the contractile response recorded. The modulatory effect of interleukin IL-1β was determined by incubating the arterial preparation with IL-1β (10 ng/ml) for 90 min before the construction of the second curve (in the continuous presence of IL-1β) for the contractile agent. Various blockers were incubated with basilar artery preparations for 30 min before the application of IL-1β (10 ng/ml). Where stated, the concentration of inhibitors used in this study was the reported effective concentration of the individual agent, based on our previous studies with different vascular smooth muscle preparations (Au et al., 2003; Choy et al., 2002; Kwan et al., 1999).
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2.4. Chemicals Physiological salts (GR grade) for preparing Krebs' solution for isometric tension measurement were obtained from Merck (Darmstadt, Germany). Interleukin-1β (human, recombinant) was purchased from PeproTech (U.K.). 5-Hydroxytryptamine hydrochloride, acetylcholine hydrochloride, L-phenylephrine hydrochloride, indomethacin, cyclohexamide and zinc protoporphyrin were obtained from Sigma-Aldrich Chemicals Co. (U.S.A.). Prazosin hydrochloride and yohimbine hydrochloride were purchased from Tocris (U.K.). 9,11-Dideoxy-9α,11αmethanoepoxy-prostaglandin F2α (U46619), 2′-amino-3′methoxyflavone (PD98059), (−)-perillic acid, tetrodotoxin
and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) were obtained from Calbiochem-Novabiochem. Incorp. (U.S.A.). 2.5. Statistical analysis Data are expressed as means ± S.E.M.; n refers to the number of rats from which the basilar artery was taken for isometric tension measurements. Statistical analysis of raw data (i.e. tension developed in millinewton) was performed using Student's paired (two-way) t-test and analysis of variance (ANOVA), where appropriate. Differences were considered to be statistically significant at a value of P b 0.05.
Fig. 1. (A) Typical recordings of U46619-induced contraction of isolated basilar artery (endothelium intact) from Sprague–Dawley rats in the absence and the presence of interleukin IL-1β (10 ng/ml, 90-min incubation). Calibration bars: 2 mN and 10 min. (B) A comparison of U46619 (30 and 100 nM)-induced contraction (in mN) recorded with (close symbols: ●, ♦) (n = 6) and without (open symbols: ○, ⋄) (n = 6) IL-1β (10 ng/ml, 90-min incubation). (C) For illustration, cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, n = 6) IL-1β (10 ng/ml, 90-min incubation) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats are presented. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control.
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3. Results Under resting tension, cumulative application of IL-1β (0.1 to 30 ng/ml) and phenylephrine (0.1 nM to 100 μM) did not alter the basal tone of isolated basilar artery (endothelium intact, n = 6; endothelium denuded, n = 6) (data not shown). However, U46619 (10–100 nM), high [K+]o (10–40 mM) (EC50 = 27.33 mM; Emax = 4.35 ± 2.05 mN) and 5-hydroxytryptamine (5-HT, 1 nM–3 μM) (EC50 = 0.1 μM; Emax = 7.54 ± 1.63 mN) elicited a concentration-dependent contraction of isolated basilar artery (endothelium intact, under resting tension) (data not shown). IL-1β (10 ng/ml, 90-min incubation) moderately potentiated the U46619 (30 and 100 nM)-elicited basilar artery (endothelium intact) contraction (n = 6) (P b 0.05 compared to control) (Fig. 1A). An approximately 0.5 log unit leftward shift (Fig. 1B) with an increased (∼50%) maximum contraction (at 100 nM) of the concentration–response curve for U46619 was observed (Fig. 1C). The IL-1β (10 ng/ml)-mediated potentiation persisted after endothelium denudation (n = 4) (data not shown). In contrast, IL-1β (10 ng/ml) failed to alter the high [K+]o(EC 50 = 29.33 mM; E max = 4.08 ± 1.36 mN) and 5-HT-
Fig. 2. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus tetrodotoxin (100 nM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration–response curves for the effect of U46619 (0.1– 100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus zinc protoporphyrin (3 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
Fig. 3. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) (○, n = 6) (control), and in the presence of IL-1β (10 ng/ml) (●, n = 6), phenylephrine (0.1 nM) (⋄, n = 6), IL-1β (10 ng/ml) plus prazosin (1 μM) (▴, n = 6) and phenylephrine (0.1 nM) plus prazosin (1 μM) (O, n = 6) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration– response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus yohimbine (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (without IL-1β, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
(EC50 = 0.1 μM; Emax = 7.08 ± 1.37 mN) elicited basilar artery contraction (endothelium intact). Application of tetrodotoxin (TTX) (100 nM) (n = 6) (Fig. 2A) eradicated, whereas zinc protoporphyrin (ZnPP) (3 μM, n = 6) (Fig. 2B) partly reduced, the IL-1β-mediated potentiation effect. A higher concentration of ZnPP (10 μM) was also tested but it markedly suppressed the U46619-elicited contraction (n = 5) (data not shown). Prazosin (1 μM, an α1adrenoceptor blocker, n = 6) (Fig. 3A), but not yohimbine (1 μM, an α2-adrenoceptor blocker, n = 6) (Fig. 3B), eradicated the IL-1β-mediated potentiation of the U46619-elicited basilar artery (endothelium intact) contraction. Tetrodotoxin (n = 6), prazosin (n = 6) or yohimbine (n = 6), applied alone, did not modify the U46619-induced basilar artery contraction (data not shown). Phenylephrine (0.1 nM), applied alone, caused potentiation of the U46619-elicited basilar artery (endothelium intact) contraction (n = 6) (Fig. 3A). Higher concentrations of phenylephrine (1 nM, n = 5; 10 nM, n = 5) caused no further enhancement (compared to 0.1 nM phenylephrine) of the U46619-mediated basilar artery contraction (data not shown). In addition, the phenylephrine (0.1 nM)-mediated potentiation
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of the U46619-elicited basilar artery contraction was sensitive to prazosin (1 μM, n = 6) (Fig. 3A). Administration of PD98059 (0.3 μM) (Fig. 4A), (−)-perillic acid (1 μM) (Fig. 4B) and SB203580 (1 μM) (Fig. 4C) inhibited the IL-1β-mediated potentiation of the contraction. PD98059 (0.3 μM) (n = 6), SB203580 (1 μM) (n = 6) or
(−)-perillic acid (1 μM) (n = 6), applied alone, did not alter the basal resting tension and the U46619-induced basilar artery (endothelium intact) contraction. In contrast, cyclohexamide (1 μM) (n = 5) (data not shown) and indomethacin (1 μM) (n = 5) (data not shown) had no apparent effect on the IL-1β-mediated potentiation of the U46619-induced contraction of basilar artery (endothelium intact). Indomethacin or cyclohexamide, applied alone, did not alter the U46619-induced basilar artery contraction (in both endothelium intact and denuded preparations) (n = 5–6) or the resting tension of basilar artery (n = 5–6) (data not shown). 4. Discussion
Fig. 4. (A) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus PD98059 (0.3 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (B) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL-1β (10 ng/ml) plus (−)-perillic acid (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○). (C) Cumulative concentration–response curves for the effect of U46619 (0.1–100 nM) with (●, n = 6) and without (○, control, n = 6) a combination of IL1β (10 ng/ml) plus SB203580 (1 μM) on contractions of isolated basilar artery (endothelium intact) from Sprague–Dawley rats. Contractions recorded were normalized to the contraction elicited by 100 nM U46619 (control, ○). Results are expressed as means ± S.E.M. ⁎P b 0.05 compared to control (○).
The major findings of this study demonstrate that a thromboxane A2 mimetic (U46619), 5-hydroxytryptamine (5-HT) and high [K+ ]o but not phenylephrine (an α1adrenoceptor agonist), elicit a concentration-dependent contraction of rat isolated basilar artery under resting tension, as observed in vivo (Fujii et al., 1990). Our results are consistent with those of previous studies (Houston and Vanhoutte, 1986; Uddman et al., 1999) in which the release of both thromboxane A2 and 5-HT was found to be important in physiological and pathophysiological conditions affecting the cerebral circulation (Satoh et al., 1991). In contrast to previous studies (Boulanger et al., 1994; Tsang et al., 2004), phenylephrine (10 nM to 100 μM) failed to cause contraction of the rat isolated basilar artery. This may be due to the use of “different gas mixtures” and the difference of pO2 measured in the organ bath. In our study, we used a gas mixture of 16% O2/6% CO2 (balanced with N2) (MacLean et al., 1996; Au et al., 2003), which provided a physiological pO2 ∼ 100 mm Hg (Takada et al., 2001) in the organ bath. However, in the other study in which phenylephrine caused basilar artery contraction in vitro (Tsang et al., 2004), experiments were performed under non-physiological hyperoxic conditions (i.e. a gas mixture of 95% O2/5% CO2, pO2 N 500 mm Hg) (Kwan et al., 1989). The basilar artery is highly sensitive to pO2 in vitro and in vivo. In our study, incubation for 90 min with IL-1β (10 ng/ml, a level that can be detected during cerebral ischaemia/stroke) (Legos et al., 2000) significantly enhanced the U46619-elicited basilar artery contraction. More importantly, zinc protoporphyrin (ZnPP) (3 μM, a putative IL-1 receptor antagonist) (Yamasaki et al., 1995) suppressed, but did not abolish, the IL-1β-mediated potentiation of the U46619-induced basilar artery contraction. A higher concentration of ZnPP (10 μM) resulted in a marked suppression of the U46619-induced contraction, suggesting that ZnPP may have another effect (such as activation of guanylase cyclase), as reported previously (Luo and Vincent, 1994). Nevertheless, our results suggest that activation of IL-1 receptors may probably be involved in the IL1β-mediated potentiation of the basilar artery contraction elicited by U46619. In anaesthetized dogs (Osuka et al., 1997), intra-cisternal administration of interleukin IL-1β (0.03 and 0.3 μg) dilated the basilar artery in a dose-dependent, ZnPP (30 μg)-sensitive manner. However, in our study with rat isolated basilar artery,
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application of IL-1β (1–30 ng/ml, 90-min incubation) did not alter the basal tone of the preparations. The underlying mechanism responsible for the discrepancy is not known, but it may be related to the species and the concentration/dose of IL1β used in these studies. The presence of functional endothelium is not important because mechanical removal of the endothelium did not modify the IL-1β (1–30 ng/ml, 90-min incubation)-mediated effect, and no apparent change in basal tone of basilar artery was observed. Interestingly, the IL-1β-mediated potentiation of basilar artery contraction was “selective” as neither high [K+]o- nor 5-HT-induced basilar artery contraction was affected by incubation with IL-1β. The underlying mechanism responsible for the differential enhancement by IL-1β of basilar artery contraction is not known. It may be related to different cellular signalling mechanisms involved in high [K+]o- and 5HT-induced vasoconstriction (Tasaki et al., 2003). In most previous studies (Pickker et al., 2002; Takizawa et al., 1998; Touzani et al., 1999), application of IL-1β generally resulted in a suppression, rather than a potentiation, of the contractile response of different blood vessels. Our novel results, for the first time, indicate that incubation with IL-1β resulted in an enhancement of U46619-elicited basilar artery contraction, which may be important in the development of stroke. It is well documented that cerebral arteries of different species are highly innervated (Bunc et al., 2001; El-Assouad and Tayebati, 2002; Handa et al., 1993; Tsai et al., 1989), and that neurotransmitters released from nerve terminals are important for maintaining the vasomotor tone of the cerebral circulation. In order to delineate the underlying mechanisms involved in the IL-1β-mediated potentiation of the U46619induced basilar artery contraction, we considered the possible release of neurotransmitter(s) from nerve terminals. The presence of tetrodotoxin (100 nM, a neuronal Na+ channel blocker) eradicated the IL-1β-mediated potentiation of the response, suggesting that the neuronal release of substance(s) from nerve terminals upon the application of IL-1β probably plays an obligatory role. As in vas deferens preparations (Trachte, 1986), the chemical (s) released from neurons following IL-1β application were identified by using different pharmacological tools. Prazosin (1 μM, an α1-adrenoceptor antagonist), but not yohimbine (1 μM, an α2-adrenoceptor antagonist), abolished the IL-1βmediated potentiation. Phenylephrine (0.1 nM, an α1-adrenoceptor agonist) applied alone mimicked the potentiation by IL1β, and the enhancement of the U46619-induced contraction observed was prevented by prazosin. It is important to appreciate that neuronally released α1-adrenoceptor agonist and exogenous phenylephrine only play a modulatory role, rather than exert a “direct vascular effect”, on rat basilar artery: phenylephrine (0.1, 1, 10, 30 and 100 nM) and IL-1β (10 ng/ml), applied alone, did not alter the basal tone of rat isolated basilar artery. Taken together, our results suggest that IL-1β (10 ng/ml) causes the release of a substance from nerve terminals that acts on α1adrenoceptors and subsequently causes an enhancement of U46619-induced basilar artery contraction.
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In addition to the well-documented role in cellular proliferation (Lin et al., 2005), the mitogen-activated protein kinase (MAPK) cascade has been suggested to have an important role in vascular smooth muscle contraction (Tasaki et al., 2003; Tsai and Jiang, 2005). In hypothalamic corticotropin-releasing neurons, IL-1β (0.25 μg/kg) induced a long-lasting increase in noradrenaline release (Schmidt et al., 2001). In rat hippocampal slices, IL-1β (3 × 10− 18–3 × 10− 14 M) triggered transportermediated [3 H]-purine efflux in a concentration-dependent manner via glutamate receptor-mediated excitatory synaptic transmission and activation of p38 MAPK (Sperlagh et al., 2004). The neuronal release of mediator(s) elicited by IL-1β in the basilar artery may involve the MAPK pathway. To explore the possible involvement of the MAPK cascade, the effect of PD98059 (a p42/44 MAPK inhibitor), (−)-perillic acid (a p21ras inhibitor) and SB203580 (a p38 MAPK inhibitor) was examined. In rat isolated basilar artery, incubation with these inhibitors, individually, attenuated the IL-1β-mediated potentiation of the U46619-elicited contraction. In contrast, it has been reported that the p38 MAPK pathway is not involved in the U46619-induced contraction of rat thoracic aorta (Tasaki et al., 2003). However, in our study, the U46619-induced contraction enhanced by IL-1β was sensitive to p38 MAPK inhibition. Taken together, our results demonstrate that the IL1β-mediated potentiation of the U46619-elicited contraction probably involves the p42/p44 and p38 MAPKs/p21 ras signalling cascade. In our study, the basilar artery was incubated with IL-1β (10 ng/ml) for 90 min before the second challenge with U46619. The possibility that protein synthesis may be responsible for the IL-1β-induced response was also considered. However, cyclohexamide (1 μM, a protein synthesis inhibitor) did not modify the IL-1β-induced response, implying that the potentiation effect probably relies on preformed substance(s) present inside the nerve terminal of the basilar artery rather than on IL-1β-induced synthesis of mediators during the incubation period. However, in anaesthetized dogs, intra-cisternal application of IL-1β caused an increase in eicosanoid concentration (Tasaki et al., 2003). Our results argue for the participation of cyclo-oxygenase cascade/ eicosanoid generation because indomethacin (1 μM, a nonselective cyclo-oxygenase inhibitor) failed to alter the IL-1βmediated potentiation of the U46619-elicited basilar artery contraction. In conclusion, our novel data demonstrate, for the first time, that IL-1β causes a selective enhancement of U46619-mediated rat basilar artery contraction, an effect that is probably mediated by the neuronal release of an α1-adrenoceptor agonist and activation of p42/p44 and p38 MAPK/p21ras pathways. Acknowledgements Mr. S.W. Seto is a recipient of a post-graduate (Ph.D.) studentship of the Department of Pharmacology (The Chinese University of Hong Kong, Hong Kong SAR, PR China). This project is supported by the RGC Earmarked Grant of Hong Kong SAR, PR China (Ref.: 4166/02M).
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References Au, A.L.S., Kwan, Y.W., Kwok, C.C., Zhang, R.Z., He, G.W., 2003. Mechanisms responsible for the in vitro relaxation of ligustrazine on porcine left anterior descending coronary artery. Eur. J. Pharmacol. 468, 199–207. Beasley, D., Cohen, R.A., Levinsky, N.G., 1989. Interleukin 1 inhibits contraction of vascular smooth muscle. J. Clin. Invest. 83, 331–335. Blake, G.J., Ridker, P.M., 2002. Inflammatory bio-markers and cardiovascular risk prediction. J. Intern. Med. 242, 283–294. Boulanger, C.M., Nakashima, M., Olmos, L., Joly, G., Vanhoutte, P.M., 1994. Effects of the Ca2+ antagonist RO 40-5967 on endotheliumdependent responses of isolated arteries. J. Cardiovasc. Pharmacol. 23, 869–876. Bunc, G., Kovacic, S., Strnad, S., 2001. Evaluation of functional response of cerebral arteries by a new morphometric technique. Auto. Neurosci. 93, 41–47. Choy, W.Y., Wong, Y.F., Kwan, Y.W., Au, A.L.S., Lau, W.H., Raymond, K., Zuo, J.Z., 2002. Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery. Eur. J. Pharmacol. 434, 55–64. Dinarello, C.A., 1997. Interleukin-1. Cytokine Growth Factor Rev. 8, 253–265. Eder, J., 1997. Tumour necrosis factor alpha and interleukin 1 signalling: do MAPKK kinases connect it all? TiPS 18, 319–322. El-Assouad, D., Tayebati, S.K., 2002. Cholinergic innervation of pial arteries in senescent rats: an immunohistochemical study. Mech. Ageing Dev. 123, 529–536. Feldman, S.R., Meyer, J.S., Quenzer, L.F., 1997. Principles of Neuropsychopharmacology. Sinauer Associates Inc., Publishers. Friberg, L., Olesen, J., Iversen, H.K., Sperling, B., 1991. Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet 338, 13–17. Fujii, K., Heistad, D.D., Faraci, F.M., 1990. Vasomotion of basilar arteries in vivo. Am. J. Physiol. 258, H1829–H1834. Gao, Y., Tang, S., Zhou, S., Ware, J.A., 2001. The thromboxane A2 receptor activates mitogen-activated protein kinase via protein kinase C-dependent Gi coupling and Src-dependent phosphorylation of the epidermal growth factor receptor. J. Pharmacol. Exp. Ther. 296, 426–433. Handa, Y., Nojyo, Y., Tamamaki, N., Tsuchida, A., Kubota, T., 1993. Development of the sympathetic innervation to the cerebral arterial system in neonatal rats as revealed by anterograde labelling with wheat germ agglutinin-horseradish peroxidase. Exp. Brain Res. 94, 216–224. Hopkins, S.J., Rothwell, N.J., 1995. Cytokines in the nervous system I: expression and recognition. TiNS 18, 83–88. Houston, D.S., Vanhoutte, P.M., 1986. Serotonin and the vascular system. Role in health and disease, and implications for therapy. Drugs 31, 149–163. Kitazono, T., Ibayashi, S., Nagao, T., Kagiyama, T., Kitayama, J., Fujishima, M., 1998. Role of tyrosine kinase in serotonin-induced constriction of the basilar artery in vivo. Stroke 29, 494–497. Kwan, Y.W., Wadsworth, R.M., Kane, K.A., 1989. Effects of hypoxia on the pharmacological responsiveness of isolated coronary artery rings from the sheep. Br. J. Pharmacol. 96, 849–856. Kwan, Y.W., To, K.W., Lau, W.M., Tsang, S.H., 1999. Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar– Kyoto rats. Eur. J. Pharmacol. 365, 241–251. LaPointe, M.C., Isenovic, E., 1999. Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p38 MAPK signalling pathways in cardiac myocytes. Hypertension 33, 276–282. Legos, J.J., Whitmore, R.G., Erhardt, J.A., Parsons, A.A., Tuma, R.F., Barone, F.C., 2000. Quantitative changes in interleukin proteins following focal stroke in the rat. Neurosci. Lett. 282, 189–192. Lin, X., Ramamurthy, S.K., Le Breton, G.C., 2005. Thromboxane a receptormediated cell proliferation, survival and gene expression in oligodendrocytes. J. Neurochem. 93, 257–268. Luo, D., Vincent, S.R., 1994. Metalloporphyrins inhibits nitric oxide dependent cGMP formation in vivo. Eur. J. Pharmacol. 267, 263–267.
MacLean, M.R., Sweeney, G., Baird, M., McCulloch, K.M., Houslay, M., Morecroft, I., 1996. 5-Hydroxytryptamine receptors mediated vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats. Br. J. Pharmacol. 119, 917–930. Matrougui, K., Maclouf, J., Levy, B.I., Henrion, D., 1997. Impaired nitric oxideand prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats. Hypertension 30, 942–947. Morgan, L., Humphrines, S.E., 2005. The genetic of stroke. Curr. Opin. Lipidol. 16, 193–199. Murray, M.A., Faraci, F.M., Heistad, D.D., 1992. Role of protein kinase C in constrictor responses of the rat basilar artery in vivo. J. Physiol. 445, 169–179. Murtha, Y.M., Allen, B.M., James, A.O., 1999. The role of protein kinase C in thromboxane A2-induced pulmonary artery vasoconstriction. J. Biomed. Sci. 6, 293–295. Narumiya, S., Sugimoto, Y., Ushikubi, F., 1999. Prostanoid receptors: structures, properties, and functions. Physiol. Rev. 79, 1193–1226. Noll, G., Luscher, T.F., 1998. The endothelium in acute coronary syndromes. Eur. Heart J. 19, C30–C38. Osuka, K., Suzuki, Y., Watanabe, Y., Dogan, A., Takayasu, M., Shibuya, M., Yoshida, J., 1997. Vasodilator effects on canine basilar artery induced by intracisternal interleukin-1 beta. J. Cereb. Blood Flow Metab. 17, 1337–1345. Pickker, P., Netea, M.G., Van der Meer, J.W.M., Smits, P., 2002. TNF and IL-1 exert no direct vasoactivity in human isolated resistance arteries. Cytokine 20, 244–246. Robert, R., Chapelain, B., Neliat, G., 1993. Different effects of IL-1 on reactivity of arterial vessels isolated from various vascular beds in the rabbit. Circ. Shock 40, 139–143. Rothwell, N.J., 1999. Cytokines — killers in the brain? J. Physiol. 514, 3–17. Rothwell, H.J., Luheshi, G.N., 1994. Pharmacology of interleukin-1 actions in the brain. Adv. Pharmacol. 25, 1–20. Rothwell, N.J., Loddick, S.A., Stroemer, P., 1997. Interleukins and cerebral ischaemia. Int. Rev. Neurobiol. 40, 281–298. Saklatvala, J., Rawlinson, L., Waller, R.J., Sarsfield, S., Lee, J.C., Barnes, M.J., Farndale, R.W., 1996. Role of p38 mitogen-activated protein kinase caused by collagen or a thromboxane analogue. J. Biol. Chem. 271, 6586–6589. Salomone, S., Morel, N., Godfraind, T., 1997. Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats. Br. J. Pharmacol. 121, 1051–1058. Satoh, S., Suzuki, Y., Harada, T., Ikegaki, I., Asano, T., Shibuya, M., Sugita, K., Saito, A., 1991. The role of platelets in the development of cerebral vasospasm. Brain Res. Bull. 27, 663–668. Schmidt, E.D., Schoffelmeer, A.N.M., De Vries, T.J., Wardeh, G., Dogterom, G., Bol, J.G., Binnekade, R., Tilders, F.J., 2001. A single administration of interleukin-1 or amphetamine induces long-lasting increases in evoked noradrenaline release in the hypothalamus and sensitization of ACTH and corticosterone responses in rats. Eur. J. Neurosci. 13, 1923–1930. Sperlagh, B., Baranyi, M., Hasko, G., Vizi, S.E., 2004. Potent effect of interleukin-1β (to evoke ATP and adenosine release from rat hippocampal slices. J. Neuroimmunol. 151, 33–39. Takada, J., Ibayashi, S., Nagao, T., Ooboshi, H., Kitazono, T., Fujishima, M., 2001. Bradykinin mediates the acute effect of an angiotensin-converting enzyme inhibitor on cerebral autoregulation in rats. Stroke 32, 1216–1219. Takizawa, S., Izaki, H., Karaki, H., 1998. Possible involvement of K+ channel opening to the interleukin-1 beta — induced inhibition of vascular smooth muscle contraction. J. Vet. Med. Sci. 61, 357–360. Tasaki, K., Hori, M., Ozaki, H., Karaki, H., Wakabayashi, I., 2003. Difference in signal transduction mechanisms involved in 5-hydroxytryptamine- and U46619-induced vasoconstriction. J. Smooth Muscle Res. 39, 107–117. Touzani, O., Boutin, H., Chuquent, J., Rothwell, N., 1999. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J. Neuroimmunol. 100, 203–215. Trachte, G.J., 1986. Thromboxane agonist (U46619) potentiates norepinephrine efflux from adrenergic nerves. J. Pharmacol. Exp. Ther. 237, 473–477. Tsai, M.H., Jiang, M.J., 2005. Extracellular signal-regulated kinase 1/2 in contraction of vascular smooth muscle. Life Sci. 76, 877–888.
S.W. Seto et al. / European Journal of Pharmacology 531 (2006) 238–245 Tsai, S.H., Tew, J.M., Shipley, M.T., 1989. Cerebral arterial innervation: II. Development of calcitonin-gene-related peptide and norepinephrine in the rat. J. Comp. Neurol. 279, 1–12. Tsang, S.Y., Yao, X., Essin, K., Wong, C.M., Chan, F.L., Gollasch, M., Huang, Y., 2004. Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels. Stroke 35, 1709–1714. Uddman, E., Moller, S., Adner, M., Edvinsson, L., 1999. Cytokines induce endothelin ETB receptor-mediated contraction. Eur. J. Pharmacol. 376, 223–232. Vicaut, E., Rasetti, C., Baudry, N., 1996. Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotension II in rat aorta. J. Appl. Physiol. 80, 1891–1897. Vila, E., Salaices, M., 2004. Cytokines and vascular reactivity in resistance arteries. J. Physiol. 288, H1016–H1021. Virids, A., Schiffrin, E.L., 2003. Vascular inflammation: a role in vascular disease in hypertension? Curr. Opin. Nephrol. Hypertens. 12, 181–187.
245
Von der Thusen, J.H., Kuiper, J., Van Berkel, T.J.C., Biessen, E.A.L., 2003. Interleukins in atherosclerosis: molecular pathways and therapeutic potential. Pharmacol. Rev. 55, 133–166. Watts, S.W., Yeum, C.H., Campbell, G., Webb, R.C., 1996. Serotonin stimulates protein tyrosyl phosphorylation and vascular contraction via tyrosine kinase. J. Vasc. Res. 33, 288–298. White, L.R., Juul, L., Skaanes, K.O., Aasly, J., 2000. Cytokine enhancement of endothelium ETB receptor-mediated contraction in human temporal artery. Eur. J. Pharmacol. 406, 117–122. Yabuuchi, K., Minami, M., Katsumata, S., Yamasaki, A., Satoh, M.A., 1994. An in situ hybridization study of interleukin-1 beta induced by transient forebrain ischaemia in the rat brain. Mol. Brain Res. 26, 135–142. Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., Kogure, K., 1995. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke 26, 676–681.