Renal hemodynamic and excretory responses to renin inhibition induced by A-64662

Experiments were conducted in sodium-depleted anesthetized monkeys to determine the effects of the primate-selective renin inhibitor A-64662 on renal function. Five groups of monkeys were examined with each group receiving an i.v. infusion of vehicle or A-64662 at doses (bolus plus continuous infusion) of 0.1 + 0.01, 1.0 + 0.1, 10 + 1.0 or 100 micrograms/kg + 10 micrograms/kg/min (n = 6/dose). Plasma renin activity was inhibited (P less than .05) at all infusion doses ranging from 33 +/- 8% at the lowest dose to 95 +/- 3% at the highest dose. Inhibition of plasma renin activity was accompanied by renal vasodilation as renal blood flow (RBF) increased (P less than .05) in a dose-dependent manner beginning at the dose of 1.0 microgram/kg + 0.1 micrograms/kg/min. RBF increased 36 +/- 7% at the highest dose of A-64662 examined. Associated with the increments in RBF, renal vascular resistance progressively decreased (P less than .05) by 12 +/- 3, 31 +/- 3 and 40 +/- 6%, respectively, with increasing doses of A-64662. Glomerular filtration rate was unchanged at all doses of A-64662. As a result, a significant (P less than .05) fall in the filtration fraction was observed as the dose of A-64662 increased. Mean arterial pressure was unaffected by the two lowest doses of A-64662, but decreased (P less than 0.05) by 13 +/- 1 and 18 +/- 4 mm Hg, respectively, at the two highest doses of A-64662 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)