Endothelium-derived relaxing factor regulates renin release in vivo.
Endothelium-derived relaxing factor (EDRF), through its inhibitory second messenger guanosine 3',5'-cyclic monophosphate (cGMP), inhibits renin release in vitro. To determine whether EDRF affects renin in vivo, we tested whether EDRF synthesis inhibition could stimulate renin secretion in intact rats. Because EDRF synthesis inhibition increases blood pressure and consequently withdraws sympathetic activity (both renin inhibitory signals), we also studied the effect of L-N omega-nitroarginine methyl ester (L-NAME) when renal perfusion pressure was controlled and during beta-adrenergic blockade. Mean blood pressure (BP), heart rate (HR), and plasma renin activity (PRA) were measured in anesthetized rats before and after EDRF synthesis inhibition by a 10 mg/kg body wt bolus of L-NAME. L-NAME decreased PRA by 67% [from 11.0 +/- 2.7 to 3.7 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, n = 12; P less than 0.001], increased BP by 20 +/- 2 mmHg (P less than 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/min (P less than 0.005). We repeated our experiment in rats instrumented with an intra-aortic balloon catheter to control renal perfusion pressure and pretreated with propranolol to eliminate the beta-adrenergic effect. Under these conditions, L-NAME now increased PRA by 55% (from 6.9 +/- 1.9 to 10.8 +/- 2.6 ng ANG I.ml-1.h-1, n = 12; P less than 0.02), whereas renal perfusion pressure was unchanged (91 +/- 4 vs. 90 +/- 4 mmHg). HR increased slightly from 308 +/- 5 to 315 +/- 3 beats/min (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005246:Feedback; D006339:Heart Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012083:Renin / Q000097:blood*
D009569:Nitric Oxide; D001120:Arginine; D011433:Propranolol; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester