Rg. Evans et al., INTERACTIONS OF BLOCKADE OF NITRIC-OXIDE SYNTHASE AND ANGIOTENSIN-CONVERTING ENZYME ON RENAL-FUNCTION IN CONSCIOUS RABBITS, Journal of cardiovascular pharmacology, 24(4), 1994, pp. 542-551
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.