AJP - Regulatory, Integrative and Comparative Physiology, Vol 259, Issue 1 7-14, Copyright © 1990 by American Physiological Society
Effect of intrarenal renin inhibition on renal hemodynamics and excretory function
K. M. Verburg, J. R. Kadam, G. A. Young, S. H. Rosenberg and H. D. Kleinert
Cardiovascular Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
This study was designed to investigate in sodium-depleted monkeys the renal
hemodynamic and excretory effects resulting from blockade of the
renin-angiotensin system induced by intrarenal infusion of the
primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317
(n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P
less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4
ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4
ml/min, with no significant changes in mean arterial pressure (MAP) or
plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow
rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion
of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a
recovery period, the intrarenal infusion dose of A-65317 was increased to
0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/-
3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4%
inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte
excretion remained at control levels. Intrarenal infusion of vehicle (n =
6) had no significant effect on any of the variables studied. In a separate
group of monkeys, intravenous (iv) infusion of A-65317 at 0.01
microgram.kg-1.min-1 (n = 5) did not result in significant changes from
control.(ABSTRACT TRUNCATED AT 250 WORDS)
