INTERACTIONS OF BLOCKADE OF NITRIC-OXIDE SYNTHASE AND ANGIOTENSIN-CONVERTING ENZYME ON RENAL-FUNCTION IN CONSCIOUS RABBITS

We tested the effects and interactions of blockade of nitric oxide (NO ) synthase and angiotensin-converting enzyme (ACE) on renal function. Six rabbits were studied four times, each at 14-day intervals. The tre atments were intravenous (i.v.) vehicle, N-G-nitro-L-arginine (L-NNA) 5 mg/kg, captopril 500 mu g plus 3.3 mu g/ kg/min, or L-NNA plus capto pril. The studies were performed in random order. Arterial blood press ure (BP), heart rate (HR), and clearance of H2O, Na+, Li+, [H-3]inulin [glomerular filtration rate (GRF)], and paraaminohippuric acid (PAH, renal plasma flow) were measured for the hour before treatment and for 3 h after treatment. Renal blood flow (RBF), renal vascular conductan ce, and GFR were reduced by 36 +/- 4, 41 +/- 4, and 17 +/- 5%, respect ively, after L-NNA treatment. Although captopril did not affect these variables significantly when given alone, it completely abolished the effects of L-NNA. After L-NNA administration, sodium excretion decreas ed by 41 +/- 11%, chiefly attributable to reduced GFR, although increa sed reabsorption of sodium also contributed. The site of this increase d reabsorption was probably the proximal nephron, since Li+ reabsorpti on(a marker of proximal tubular sodium reabsorption) tended to increas e by 8.4 +/- 4.8%. Captopril had a natriuretic effect chiefly attribut able to reduced sodium reabsorption in the proximal nephron. When thes e agents were coadministered, proximal tubular sodium reabsorption did not change significantly. Our data suggest the existence of a functio nal interaction between ACE and NO synthase in control of RBF and GFR. These enzyme systems also appear to have opposing influences on proxi mal tubular sodium reabsorption, but their actions on tubular sodium h andling appear to be mutually independent.