- Email: [email protected]
Clonidine but not moxonidine shows attenuated renal effects in spontaneously hypertensive rats
CONTRAST MEDIA INDUSED ACUTE RENAL FAILURE: EFFECTS OF CALCIUM ANTAGONISTS Fatima Dz.qoeva, Dimitry Okunev, Irina Kutyrina, Vadim Menshikov, Olga Zozulya. (Moscow Medical Academy, Russia) Effects of calcium channel blockers•inischemic acute renal failure (ARF) due to contrast media were investigated. Experimental model of reversible ARF was obtained in Wistar rats by intravenous contrast media (CM) injection. Studies were performed on three groups of animals: I (contr01-group) were given the injection of isotonic saline; II group received high.:osmolality CM verografin (10 ml/kg) and III group received both CM and calcium channel blocker verapamil (1.5 mg/kg). All animals were placed on the low sodium diet for the week before the experimental manipulatior~. Level of serum creatinine, 24-hour creatinine clearance, renal blood volume, plasma electrolytes (Na, Ca), fractional excretion of sodium, plasma renin activity, serum vasopressin and aldosteron levels were determined 1 day before and 2, 3 and 14 days after CM injection. The data 3 days after injection indicate that in this model of ARF verapamil prevented the rise in serum creatinine (1.04+0.12, 2.90+0.60 and 120+0.04 mg% in I, II and III group respectively)and protected renal blood volume (0.29+0.03 in I, 0.13+0.01 in II and 0.26+0.02 ml/g in III group) and GFR. (0.94+0.01 in I, 0.46+0.01 in II and 0.79+0.06 ml/min in,Ill group). Thesedata indicate that: calcium antagonists may play an important protective role in contrast media ARF.
LOCALIZATION OF V 1AND V 2 BINDING SITES FOR AVP IN THE KIDNEY OF WISTAR KYOTO RATS. A. Czarnecki J. Brown. Drug Institute, Warsaw, Poland & Physiological Laboratory, University of Cambridge, Cambridge, England. There are at least two types of receptors for arginine vasopressin (AVP) responsible for AVP effect in the body. V2 receptors are known to evoke the antidiuretic effect of AVP in the kidney. V~ receptors were discovered on blood vessels but some subtypes were found in other tissues. The aim of this study was to localize and discriminateV1 and V 2 binding sites in the kidney using tritium-labelled AVP and V t- and V2-selective ligands respectively d(CH2)sTyrMeAVP and [d(CH=)5,D-IIe2,Ile4]AVP. Kidneys from six Wistar Kyoto rats (240-270g) were snap-frozen in isopentane. Serial 15~m sections were preincubated in phosphate buffer. They were then incubated with 10nM [3H]AVP and with or without unlabelled AVP, or V~- and V2-selective ligands either individually or together. After incubation and exposure to Hyperfilm 3H, regional binding was measured from autoradiograms. Autoradiograms revealed high affinity, low capacity, specifically reversible binding sites for 3H-AVP throughout inner and outer medulla and at much lower density in the cortex. All high affinity specifically reversible binding for AVP was displaced by AVP or Vl&V2-selective ligands added together. V2-selective ligand displaced about 80% of binding in medulla and about 60% binding in the cortex. The binding which was not inhibited by 101sm of V2-selective ligand was inhibited by 101~m of V~-selective ligand. About 40% of the binding in medulla was not displaced by V~-selective ligand. These results suggest that both types of AVP receptors are present in the kidney. Their ligands may therefore modify AVP effects in the kidney either by influencing antidiuresls or vascular tone. The presence of both high affinity binding sites for AVP in kidney could be of importance for the control of blood pressure and sodium homeostasis.
NITRIC OXIDE (NO) IN THE PATHOGENESIS OF ACUTE RENAL FAILURE (ARF)IN RATS. F.U.Dz.qoeva, Yu U Milovanov, O.V. Zozulya, I.M: Kutyrina
CLONIDINE BUT NOT MOXONIDINE SHOWS ATTENUATED RENAL EFFECTS IN SPONTANEOUSLY HYPERTENSIVE RATS
H.,. Hoha.qe, C. JaN, K. Hess, J. Greven*, E. Schlatter Medizinische Poliklinikl Albert Schweitzer Strasse 33, D48129 MQnster, and Department of Pharmacology, RWTH :Aachen*, Germany
ARF was induced by intravenous verografin injection (10 ml/kg). NO formation in (fie liver and kidney was monitored hy t h e intensity of the electrOh paramagnetic, re.
- -
Spontaneously hypertensive rats (SHR) are believed to have an altered receptor/ second messenger coupling. Since we could recently demonstrate in Sprague Dawley (SD) rats, that moxonidine exerts beside its antihypertensive properties, additional renal effects, the purpose of this study was to investigate the renal effects of imidazoline comipounds in anaesthetised SHR. ........................................................................................
moxonidine
S..H.R. ................ ..S.D. ...................
t~ Na* excretion 5.9 5.4 A urine flow 35 55.8 clonidine A Na÷ excretion 0.2# 3.1 A urine flow 0.9# 47.3 Tab.1 Effects of moxonidine (0.5 mg/kg b.w.) and clonidine (0.5 mg/kg b.w.) on A~Na÷ excretion (iJmol/min*100g b.w.) and urine flow (IJI/min*100g b.w.) in anaesthetised SHR and Sprague Dawley rats. #=p<0.05 SHR vs. Sprague Dawley rats, n=5. Our study provides evidence, that also ~2 adrenoceptors seem to have a defective second messenger coupling in SHR. Furthermore, moxonidine exerts quantitative different effects as compared to clonidine in SHR.
354
- -
LOCALIZATION OF V 1AND V 2 BINDING SITES FOR AVP IN THE KIDNEY OF WISTAR KYOTO RATS. A. Czarnecki J. Brown. Drug Institute, Warsaw, Poland & Physiological Laboratory, University of Cambridge, Cambridge, England. There are at least two types of receptors for arginine vasopressin (AVP) responsible for AVP effect in the body. V2 receptors are known to evoke the antidiuretic effect of AVP in the kidney. V~ receptors were discovered on blood vessels but some subtypes were found in other tissues. The aim of this study was to localize and discriminateV1 and V 2 binding sites in the kidney using tritium-labelled AVP and V t- and V2-selective ligands respectively d(CH2)sTyrMeAVP and [d(CH=)5,D-IIe2,Ile4]AVP. Kidneys from six Wistar Kyoto rats (240-270g) were snap-frozen in isopentane. Serial 15~m sections were preincubated in phosphate buffer. They were then incubated with 10nM [3H]AVP and with or without unlabelled AVP, or V~- and V2-selective ligands either individually or together. After incubation and exposure to Hyperfilm 3H, regional binding was measured from autoradiograms. Autoradiograms revealed high affinity, low capacity, specifically reversible binding sites for 3H-AVP throughout inner and outer medulla and at much lower density in the cortex. All high affinity specifically reversible binding for AVP was displaced by AVP or Vl&V2-selective ligands added together. V2-selective ligand displaced about 80% of binding in medulla and about 60% binding in the cortex. The binding which was not inhibited by 101sm of V2-selective ligand was inhibited by 101~m of V~-selective ligand. About 40% of the binding in medulla was not displaced by V~-selective ligand. These results suggest that both types of AVP receptors are present in the kidney. Their ligands may therefore modify AVP effects in the kidney either by influencing antidiuresls or vascular tone. The presence of both high affinity binding sites for AVP in kidney could be of importance for the control of blood pressure and sodium homeostasis.
NITRIC OXIDE (NO) IN THE PATHOGENESIS OF ACUTE RENAL FAILURE (ARF)IN RATS. F.U.Dz.qoeva, Yu U Milovanov, O.V. Zozulya, I.M: Kutyrina
CLONIDINE BUT NOT MOXONIDINE SHOWS ATTENUATED RENAL EFFECTS IN SPONTANEOUSLY HYPERTENSIVE RATS
H.,. Hoha.qe, C. JaN, K. Hess, J. Greven*, E. Schlatter Medizinische Poliklinikl Albert Schweitzer Strasse 33, D48129 MQnster, and Department of Pharmacology, RWTH :Aachen*, Germany
ARF was induced by intravenous verografin injection (10 ml/kg). NO formation in (fie liver and kidney was monitored hy t h e intensity of the electrOh paramagnetic, re.
- -
Spontaneously hypertensive rats (SHR) are believed to have an altered receptor/ second messenger coupling. Since we could recently demonstrate in Sprague Dawley (SD) rats, that moxonidine exerts beside its antihypertensive properties, additional renal effects, the purpose of this study was to investigate the renal effects of imidazoline comipounds in anaesthetised SHR. ........................................................................................
moxonidine
S..H.R. ................ ..S.D. ...................
t~ Na* excretion 5.9 5.4 A urine flow 35 55.8 clonidine A Na÷ excretion 0.2# 3.1 A urine flow 0.9# 47.3 Tab.1 Effects of moxonidine (0.5 mg/kg b.w.) and clonidine (0.5 mg/kg b.w.) on A~Na÷ excretion (iJmol/min*100g b.w.) and urine flow (IJI/min*100g b.w.) in anaesthetised SHR and Sprague Dawley rats. #=p<0.05 SHR vs. Sprague Dawley rats, n=5. Our study provides evidence, that also ~2 adrenoceptors seem to have a defective second messenger coupling in SHR. Furthermore, moxonidine exerts quantitative different effects as compared to clonidine in SHR.
354
- -