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L-arginine modulates the rat middle cerebral artery reactivity
i INVESTIGATIONS OF INFLUENCE OF MASS OF BODY, ! RESISTANCE TO ANTYHYPERTENS1VE DRUGS AND CAUSE OF HYPERTENSION ON SERUM INSULIN LEVEL IN HYPERTONICS
:LZ~Lgorowska-Staehowiak A.Chodera Dept. of Pharm., Academy of Medicine, Fredry10 Str, 61-701 Pozuafi, Poland
L-ARGININE MODULATES THE RAT MIDDLE CEREBRAL ARTERY REACTIVITY M.J. Alonso. S. Gabancho, ,J. Marfn, A, Ponte, M.C. HerMndez and M. Salaices. Dept. Farrr/acologta y Teraptutica, Fac. Medicina UAM, C/Arzobispo Morcillo 4, 28029-Madrid, Spain.
A large percentage of hypertensive patients has selective resistance to insulin (I) action and increased serum level of this hormone. Patients with HT vary in their mass of body, serum I level and their sensitivity to antyhypertensivedrugsi The aim of present study was evaluation ff mass of body, number of using antyhypertensive drugs by one patient and etiology of hypertension (essential or ,symptomatical hypertension) have separate influence on serum I level in hypertonics. There were three investigated groups: healthy people (C, n=36), essential hypertension (EH, n=38) and renovascular hypertension (RVH, n=33) (DSA performed), the mean age was about 38-42 years in every group, in ali ihypertonics RR2160/95. Groups EH and RVH were divided into two parts i ~patients who were sensitive to antyhypertensive therapy (needed < 2 drugs tO inormalize or significantly lower blood pressure) - EH - S (n=22) and RVH - S ~.(n=13)and also whose hypertension was refractory (needed > 3 drugs) - Eli - g (n=16) and RVH - R (n=20). Anthropometric measurements were made td define BMI, we chosen patients with similar BMI (25,80 - 25,91 kg/m2) iri each group. Oral glucose tolerance test (75 g) was made for everyone. Th¢~ concentration of I in serum was determined (fasting, 60 and 120 rain afief loading) with SEReNe radioimmunoassay kits. Serum I level (mU/ml) fasting (Io): C 10,98 + 1,03; EH 21,76 + 2,14; RVH 8,79 + 0,64 after lh (I1); C 52,08~ + 5,77; EH 128,02 + 11,48; RVH 54,52 + 4,14 after 2h (I2): C 26,32 + 1,87Z EH 74,23 + 6,41; RVH 28,67 + 2,19. For refractory groups: Io EH-R 21,63 2,13; Io RVH-R 8,86 + 0,80; I 1 EH-R 146,25+ 19,3; I 1 RVH-R 59,05 + 5,79;i 12EH-R 80,81 + 10,46; 12 RVH-R 32,8 + 3,23 versus sensitive groups: 1o EH-Si 21,89 + 3,41; Io RVH-S 8,73 + 1,09; I 1 EH-S 109,8 + 12,71; I 1 TVH-S 50,0 5,27; 12 EH-S 67,66 + 9,07; 12 RVI-I-S24,54 + 1,96. Refractory patients in botk Eli and RVH group have higher serum insulin level than sensitive ones, but ihese differences were not sign. statist.. Resistance to antyhypertensive therap~ does not influence I concentration significantly. Patients with EH revealeff.~ higher, statistically significant (p < 0,001), I level than the ones with RVH andi ~. There was the correlation (p < 0,05) between I 1 and BMI only in C group.! BMI !nfluences I level onlYi n healthy people~. . . . . . . .
The aim of the present study was to analyze the role of L-arginine (L-Arg) on rat middle cerebral artery (MCA) reactivity. MCAs (212.48+2.55 ~tm diameter) of six-month-old rats were isolated and mounted in an isometric Mulvany myograph. The presence of endothelium was tested by the ability of 1 ~M bradykinin to induce vasodilatation. Prostaglandin F2o~ (PGF2o0 induced contractile responses of 0.40_+0.08 mN/mm and 0.37+0.09 mN/mm in arteries with and without endothelium, respectively. Incubation with 0.1 mM LArg for 15 rain decreased the basal tone in arteries with (0.04+0.01mN/mm) and without (-0.07+0.03 mN/mm) endothelium. It also reduced the contraction induced by PGF2o~ from 33.26+3.8 to 23.3+4.30 (p<0.05) and from 38.09+3.8 to 20.78_+5.59 % (p<0.05) in arteries with and without endothelium, respectively (values are expressed in percentage of the maximum response, which corresponds to the difference between the tone obtained with 120 mM K + and that caused by 0.1 mM papaverine). K + 120 mM induced a biphasic response which reached a plateau in 10 rain. In the presence of 0.1 mM L-Arg the maximum K + response was reduced and not maintained. The NO synthase inhibitor NG-monomethyl-L-arginine (0.1 mM) increased the basal tone in arteries with (0.05_+0.01 mN/mm) and without (0.02+0.01 mN/mm)endothelium, and abolished the L-Arg-induced hyporeactivity to PGF2a and K +. The incubation of the arteries with 1 gM dexamethasone from their isolation of the brain reduced the inhibitory effect of L-Arg on the responses to PGF2c~ and K + (p<0.05). These results suggest that in rat cerebral arteries there is: (I) a deficiency of L-arginine, and (2) a NO formation from both endothelial Ceils and smooth muscle inducible NOsynthase.
:NITRIC OXIDE MODULATION OF DILATION CAUSED BY P R E S S U R E FALL IN NEW-BORN PIGLET CEREBRAL iARTERIES. :J. Martinez-Orgado*, R. Gonzfilez, M.I. Alonso , J. Redondo, J.L. LLergo and J. Marin. *Servicio de Pediatria, Hospital "Virgen de la Luz", Cuenca and Dept. Farmacologia y Terap6utica, Fac. Medicina UAM, Arzobispo Morcillo 4, 28029-Madrid, Spain.
ESSENTIAL PHOSPHOLIPIDS PREVENT TISSUE DAMAGES IN TARGET ORGANS INDUCED BY CHRONIC STRESS.
The objective of this study was to evaluate the role of nitric oxide (NO) in the vasodilatory response of piglet cerebral arteries to pressure fall. New-born piglet middle cerebral arteries Of 3-4 dayold (224,7-272 ~tm diameter) were isolated and mounted on glass cannulas in a chamber containing oxygenated Krebs-Henseleit solution at 37 ° C. Intraluminal pressure was adjusted using a syringe filled with this solution and connected to an inflow cannula. Vessel diameter change was measured in a computarized video :system. The presence of endothelium was tested by the ability of 1 ~tm bradykinin to dilate the artery precontracted with 50 mM KC1. In some segments (4 segments each), the endothelium was removed by infusing distilled water for 15 s at a flow rate of I ml/min. Then, :segments were allowed to equilibrate for 60 min, and then perfusion pressure was fallen from 30 to 10 m m Hg. The effect of 10 ~tM indomethacin, 10 IxM L-NAME, 1 ~tM methylen blue or 25 mM KC1 on the pressure reduction was studied. Some arterial segments :vasodilate after fall of the pressure up to 10 m m Hg and autoregulate between 30 and 70 m m Hg pressure (autoregulatory arteries); those did not dilate, showed a myogenic response at 50-70 rnm Hg (not autoregulatory arteries). Arteries without endothelium did not dilate after pressure fall to 10 m m Hg. Vasodilation was not affected either by indomethacin or KC1, but it was abolished by LNAME and methylen blue. The results suggest the existence of an endothelium (NO) -dependent autoregulatory mechanism which is a non generalized arterial phenomenon in new-born piglets, likely by a deficient maturation. Supported by FISS (93/0916E)
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Supported by DGICYT (PM92-0037)
M.A.Atadzhanov, G.R.Sadykova. N.S.Bashirova, A.I.Usmakhodzhaeva. Centr.Resp.Lab.Institute of Advanced Medical Studies, Parkentskaya Str, 51,700007 Tashkent, Republic o f Uzbekistan. In disadaptation phase of the chronic stress (3,5 months) in rats we revealed neuroendoctrine and metabolic disturbances manifested by: a) changes of vegetative regulation, b) glucocorticoid insufficiency, c) inhibition biosynthesis of phospholipids (PhL) and cholesterol (Ch) in li~,er and d) decreasing level of PhL in blood, in the myoeardium and arterial wall but increasing of C h in them. Treatment experimental rats with phospholipids complex, synthesized from soybean, given per os during !,5 months from second m o n t h of lasted chronic stress resulted i n increasing of serum cortisol, activation of byosynthesis of PhL and Ch in liver and normalization of concentration of PhL and C h in blood and in tissue of the target organs. We suggest that reversible character of lipid metabolism and the other disturbances during t h e chronic stress caused by increasing accepter propeties of high density lipoproteins to C h under the influence of PhL, complex which promotes normalization return delivery Ch into the liver. Thus, present results lead us to the conclusion that administration essential PhL over a long period of time may prevent tissue damages in targed organs induced by chronic stress.
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:LZ~Lgorowska-Staehowiak A.Chodera Dept. of Pharm., Academy of Medicine, Fredry10 Str, 61-701 Pozuafi, Poland
L-ARGININE MODULATES THE RAT MIDDLE CEREBRAL ARTERY REACTIVITY M.J. Alonso. S. Gabancho, ,J. Marfn, A, Ponte, M.C. HerMndez and M. Salaices. Dept. Farrr/acologta y Teraptutica, Fac. Medicina UAM, C/Arzobispo Morcillo 4, 28029-Madrid, Spain.
A large percentage of hypertensive patients has selective resistance to insulin (I) action and increased serum level of this hormone. Patients with HT vary in their mass of body, serum I level and their sensitivity to antyhypertensivedrugsi The aim of present study was evaluation ff mass of body, number of using antyhypertensive drugs by one patient and etiology of hypertension (essential or ,symptomatical hypertension) have separate influence on serum I level in hypertonics. There were three investigated groups: healthy people (C, n=36), essential hypertension (EH, n=38) and renovascular hypertension (RVH, n=33) (DSA performed), the mean age was about 38-42 years in every group, in ali ihypertonics RR2160/95. Groups EH and RVH were divided into two parts i ~patients who were sensitive to antyhypertensive therapy (needed < 2 drugs tO inormalize or significantly lower blood pressure) - EH - S (n=22) and RVH - S ~.(n=13)and also whose hypertension was refractory (needed > 3 drugs) - Eli - g (n=16) and RVH - R (n=20). Anthropometric measurements were made td define BMI, we chosen patients with similar BMI (25,80 - 25,91 kg/m2) iri each group. Oral glucose tolerance test (75 g) was made for everyone. Th¢~ concentration of I in serum was determined (fasting, 60 and 120 rain afief loading) with SEReNe radioimmunoassay kits. Serum I level (mU/ml) fasting (Io): C 10,98 + 1,03; EH 21,76 + 2,14; RVH 8,79 + 0,64 after lh (I1); C 52,08~ + 5,77; EH 128,02 + 11,48; RVH 54,52 + 4,14 after 2h (I2): C 26,32 + 1,87Z EH 74,23 + 6,41; RVH 28,67 + 2,19. For refractory groups: Io EH-R 21,63 2,13; Io RVH-R 8,86 + 0,80; I 1 EH-R 146,25+ 19,3; I 1 RVH-R 59,05 + 5,79;i 12EH-R 80,81 + 10,46; 12 RVH-R 32,8 + 3,23 versus sensitive groups: 1o EH-Si 21,89 + 3,41; Io RVH-S 8,73 + 1,09; I 1 EH-S 109,8 + 12,71; I 1 TVH-S 50,0 5,27; 12 EH-S 67,66 + 9,07; 12 RVI-I-S24,54 + 1,96. Refractory patients in botk Eli and RVH group have higher serum insulin level than sensitive ones, but ihese differences were not sign. statist.. Resistance to antyhypertensive therap~ does not influence I concentration significantly. Patients with EH revealeff.~ higher, statistically significant (p < 0,001), I level than the ones with RVH andi ~. There was the correlation (p < 0,05) between I 1 and BMI only in C group.! BMI !nfluences I level onlYi n healthy people~. . . . . . . .
The aim of the present study was to analyze the role of L-arginine (L-Arg) on rat middle cerebral artery (MCA) reactivity. MCAs (212.48+2.55 ~tm diameter) of six-month-old rats were isolated and mounted in an isometric Mulvany myograph. The presence of endothelium was tested by the ability of 1 ~M bradykinin to induce vasodilatation. Prostaglandin F2o~ (PGF2o0 induced contractile responses of 0.40_+0.08 mN/mm and 0.37+0.09 mN/mm in arteries with and without endothelium, respectively. Incubation with 0.1 mM LArg for 15 rain decreased the basal tone in arteries with (0.04+0.01mN/mm) and without (-0.07+0.03 mN/mm) endothelium. It also reduced the contraction induced by PGF2o~ from 33.26+3.8 to 23.3+4.30 (p<0.05) and from 38.09+3.8 to 20.78_+5.59 % (p<0.05) in arteries with and without endothelium, respectively (values are expressed in percentage of the maximum response, which corresponds to the difference between the tone obtained with 120 mM K + and that caused by 0.1 mM papaverine). K + 120 mM induced a biphasic response which reached a plateau in 10 rain. In the presence of 0.1 mM L-Arg the maximum K + response was reduced and not maintained. The NO synthase inhibitor NG-monomethyl-L-arginine (0.1 mM) increased the basal tone in arteries with (0.05_+0.01 mN/mm) and without (0.02+0.01 mN/mm)endothelium, and abolished the L-Arg-induced hyporeactivity to PGF2a and K +. The incubation of the arteries with 1 gM dexamethasone from their isolation of the brain reduced the inhibitory effect of L-Arg on the responses to PGF2c~ and K + (p<0.05). These results suggest that in rat cerebral arteries there is: (I) a deficiency of L-arginine, and (2) a NO formation from both endothelial Ceils and smooth muscle inducible NOsynthase.
:NITRIC OXIDE MODULATION OF DILATION CAUSED BY P R E S S U R E FALL IN NEW-BORN PIGLET CEREBRAL iARTERIES. :J. Martinez-Orgado*, R. Gonzfilez, M.I. Alonso , J. Redondo, J.L. LLergo and J. Marin. *Servicio de Pediatria, Hospital "Virgen de la Luz", Cuenca and Dept. Farmacologia y Terap6utica, Fac. Medicina UAM, Arzobispo Morcillo 4, 28029-Madrid, Spain.
ESSENTIAL PHOSPHOLIPIDS PREVENT TISSUE DAMAGES IN TARGET ORGANS INDUCED BY CHRONIC STRESS.
The objective of this study was to evaluate the role of nitric oxide (NO) in the vasodilatory response of piglet cerebral arteries to pressure fall. New-born piglet middle cerebral arteries Of 3-4 dayold (224,7-272 ~tm diameter) were isolated and mounted on glass cannulas in a chamber containing oxygenated Krebs-Henseleit solution at 37 ° C. Intraluminal pressure was adjusted using a syringe filled with this solution and connected to an inflow cannula. Vessel diameter change was measured in a computarized video :system. The presence of endothelium was tested by the ability of 1 ~tm bradykinin to dilate the artery precontracted with 50 mM KC1. In some segments (4 segments each), the endothelium was removed by infusing distilled water for 15 s at a flow rate of I ml/min. Then, :segments were allowed to equilibrate for 60 min, and then perfusion pressure was fallen from 30 to 10 m m Hg. The effect of 10 ~tM indomethacin, 10 IxM L-NAME, 1 ~tM methylen blue or 25 mM KC1 on the pressure reduction was studied. Some arterial segments :vasodilate after fall of the pressure up to 10 m m Hg and autoregulate between 30 and 70 m m Hg pressure (autoregulatory arteries); those did not dilate, showed a myogenic response at 50-70 rnm Hg (not autoregulatory arteries). Arteries without endothelium did not dilate after pressure fall to 10 m m Hg. Vasodilation was not affected either by indomethacin or KC1, but it was abolished by LNAME and methylen blue. The results suggest the existence of an endothelium (NO) -dependent autoregulatory mechanism which is a non generalized arterial phenomenon in new-born piglets, likely by a deficient maturation. Supported by FISS (93/0916E)
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Supported by DGICYT (PM92-0037)
M.A.Atadzhanov, G.R.Sadykova. N.S.Bashirova, A.I.Usmakhodzhaeva. Centr.Resp.Lab.Institute of Advanced Medical Studies, Parkentskaya Str, 51,700007 Tashkent, Republic o f Uzbekistan. In disadaptation phase of the chronic stress (3,5 months) in rats we revealed neuroendoctrine and metabolic disturbances manifested by: a) changes of vegetative regulation, b) glucocorticoid insufficiency, c) inhibition biosynthesis of phospholipids (PhL) and cholesterol (Ch) in li~,er and d) decreasing level of PhL in blood, in the myoeardium and arterial wall but increasing of C h in them. Treatment experimental rats with phospholipids complex, synthesized from soybean, given per os during !,5 months from second m o n t h of lasted chronic stress resulted i n increasing of serum cortisol, activation of byosynthesis of PhL and Ch in liver and normalization of concentration of PhL and C h in blood and in tissue of the target organs. We suggest that reversible character of lipid metabolism and the other disturbances during t h e chronic stress caused by increasing accepter propeties of high density lipoproteins to C h under the influence of PhL, complex which promotes normalization return delivery Ch into the liver. Thus, present results lead us to the conclusion that administration essential PhL over a long period of time may prevent tissue damages in targed organs induced by chronic stress.
235 --