BRADYKININ CONTRIBUTION TO RENAL BLOOD-FLOW EFFECT OF ANGIOTENSIN CONVERTING-ENZYME-INHIBITOR IN THE CONSCIOUS SODIUM-RESTRICTED DOG

We examined the relative contribution of renin-angiotensin system blockade and bradykinin potentiation to the renal hemodynamic effect of the angiotensin converting enzyme inhibitor enalaprilat in sodium-deprived dogs. Six conscious dogs instrumented for monitoring of blood pressure (BP) and renal blood flow (RBF) were employed in five groups of experiments. In group 1, enalaprilat alone was administered, and it decreased BP by -24 ± 3 mm Hg and increased RBF by 135 ± 15 ml/min. During a constant intravenous infusion of saralasin (group 2), enalaprilat decreased BP by -7 ± 3 mm Hg and increased RBF by 84 ± 7 ml/min (ΔBP and ΔRBF, p < 0.01 vs. group 1 by analysis of variance). During a constant intrarenal arterial infusion of saralasin (group 3), the respective changes in BP and RBF after enalaprilat were -10 ± 3 mm Hg and 69 ± 12 ml/min, and these results did not differ from those of group 2. The infusion of saralasin intravenously or intrarenal arterially decreased BP slightly and increased RBF. In the presence of an intravenous infusion of a specific bradykinin antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg·TFA (B5630) (group 4), enalaprilat decreased BP by -28 ± 4 mm Hg and increased RBF by 82 ± 24 ml/min (ΔRBF, p 0.01 vs. group 1). The largest attenuation of the RBF increase to enalaprilat was seen in group 5, in which intravenous saralasin and intrarenal arterial B5630 were administered concurrently; the BP decrease was -10 ± 4 mm Hg, and RBF increase was 38 ± 7 ml/min (ΔRBF, p < 0.01 vs. group 1, p < 0.05 vs. groups 2 and 4). The results clearly indicate that while blockade of the renin-angiotensin system accounted for a significant part of the increase in RBF caused by an angiotensin converting enzyme inhibitor, a substantial component was contributed by endogenous bradykinin.