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 treatments were intravenous (i.v.) vehicle, NG-nitro-L-arginine (L-NNA) 5 mg/kg, captopril 500 micrograms plus 3.3 micrograms/kg/min, or L-NNA plus captopril. The studies were performed in random order. Arterial blood pressure (BP), heart rate (HR), and clearance of H2O, Na+, Li+, [3H]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 conductance, and GFR were reduced by 36 +/- 4, 41 +/- 4, and 17 +/- 5%, respectively, 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 decreased by 41 +/- 11%, chiefly attributable to reduced GFR, although increased reabsorption of sodium also contributed. The site of this increased reabsorption was probably the proximal nephron, since Li+ reabsorption (a marker of proximal tubular sodium reabsorption) tended to increase by 8.4 +/- 4.8%. Captopril had a natriuretic effect chiefly attributable to reduced sodium reabsorption in the proximal nephron. When these agents were coadministered, proximal tubular sodium reabsorption did not change significantly. Our data suggest the existence of a functional interaction between ACE and NO synthase in control of RBF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Evans
R G
RG
Emily E. E. Stewart Renal Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Rankin
A J
AJ
Anderson
W P
WP
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D002216:Captopril / Q000097:blood / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D008094:Lithium / Q000097:blood / Q000652:urine; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D011188:Potassium / Q000097:blood / Q000652:urine; D011817:Rabbits; D011897:Random Allocation; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D019335:Nitroarginine; D001120:Arginine; C009727:benzoylarginine ethyl ester; D008094:Lithium; D002216:Captopril; D012964:Sodium; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007703:Peptidyl-Dipeptidase A; D011188:Potassium