Potentiation of the renal responses to bradykinin by inhibition of neutral endopeptidase 3.4.24.11 and angiotensin-converting enzyme in anesthetized dogs

AA Seymour, JH Sheldon, PL Smith, M Asaad and WL Rogers

Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey.

The renal vascular and excretory responses to intrarenal bradykinin were obtained in anesthetized dogs receiving the angiotensin-converting enzyme inhibitor, captopril, and the neutral endopeptidase inhibitor SQ 28,603 (N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-alanine) given individually and together. Intrarenal bradykinin injections of 0.1, 1 and 10 ng/kg, respectively, increased the area over the curve of the renal blood flow response (RBF) by 6 +/- 2, 15 +/- 2 and 101 +/- 8 ml, respectively, sodium excretion by 0.6 +/- 0.4, 2.9 +/- 0.5 and 21.8 +/- 1.3 microEq/min, respectively and urinary cyclic GMP excretion by 23 +/- 12, 56 +/- 22 and 210 +/- 35 pmol/min, respectively. After 10 mumol/kg i.v. of captopril, area over the RBF curve increased by 5 +/- 4, 30 +/- 6 (P < .05) and 142 +/- 14 ml (P < .05), respectively. Captopril also significantly prolonged the sodium response to 10 ng/kg of bradykinin although the peak natriuretic activity (32 +/- 5 microEq/min) was not significantly different from the natriuresis obtained under control conditions (22 +/- 1 microEq/min). In contrast, 30 mumol/kg i.v. of SQ 28,603 increased only the peak natriuretic responses to 1.1 +/- 3.9 (P < .05), 12.1 +/- 8.4 and 40.4 +/- 12.4 (P < .05) microEq/min without prolonging the sodium response or affecting the vascular activity of bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 269, Issue 1, pp. 263-270, 04/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics