ENDOTHELIUM-DERIVED RELAXING FACTOR REGULATES RENIN RELEASE INVIVO

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 < 0.001], increased BP by 20 +/- 2 mmHg (P < 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/min (P < 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 < 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 < 0.005). These results suggest that, when changes in renal perfusion pressure and beta-adrenergic activity are controlled, EDRF synthesis inhibition with L-NAME results in an increase in PRA. Therefore tonic release of EDRF from the renal endothelium, presumably through the inhibitory second messenger cGMP, may serve as an inhibitory modulator of renin release in the whole animal.