Interactions of blockade of nitric oxide synthase and angiotensin-converting enzyme on renal function in conscious rabbits

Roger G. Evans, Andrew J. Rankin, Warwick P. Anderson

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Abstract

We tested the effects and interactions of blockade of nitric oxide (NO) synthase and angiotensinconverting 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 xg plus 3.3 xg 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. These enzyme systems also appear to have opposing influences on proximal tubular sodium reabsorption, but their actions on tubular sodium handling appear to be mutually independent.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume24
Issue number4
Publication statusPublished - 1994
Externally publishedYes

Keywords

  • Angiotensin converting enzyme
  • Conscious rabbit
  • Glomerular filtration
  • Nitric oxide
  • Renal blood flow
  • Sodium reabsorption

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