CHRONIC INHIBITION OF BRADYKININ B-2-RECEPTORS ENHANCES THE SLOW VASOPRESSOR RESPONSE TO ANGIOTENSIN-II

The contribution of endogenous kinins in the regulation of blood press ure of angiotensin-treated rats was evaluated using the new bradykinin B-2-receptor antagonist Hoe 140 D-Arg,[Hyp(3),Thi(5),D-Tic(7),Oic(8)] -bradykinin). Chronic infusion of Hoe 140 at 75 nmol/d (a dose able to inhibit the vasodepressor effect of an intra-aortic bolus injection o f 0.85 nmol/kg bradykinin) did not alter systolic blood pressure (tail -cuff plethysmography). Chronic infusion of angiotensin II (Ang II) in duced a dose-related increase in systolic blood pressure and plasma An g II levels. The vasopressor effect of 40 or 100 nmol/d Ang II was enh anced in rats given chronic infusion of Hoe 140 (by 12 and 14 mm Hg, r espectively), whereas the increase in plasma Ang II levels remained un altered. Furthermore, a low nonpressor dose of Ang II (20 nmol/d) was then able to increase blood pressure during chronic blockade of bradyk inin receptors by Hoe 140 (from 126 +/- 3 to 137 +/- 3 mm Hg, P < .05) . Combined infusion of 20 nmol Ang II and Hoe 140 did not alter the ur inary excretion of sodium and water despite the fact that blood pressu re was increased. Potentiation of the pressure effect of Ang II by Hoe 140 was confirmed by direct measurement of mean blood pressure (125 /- 2 versus 108 +/- 2 mm Hg at 20 nmol, 123 +/- 2 versus 110 +/- 2 mm Hg at 40 nmol, and 139 +/- 2 versus 125 +/- 3 mm Hg at 100 nmol Ang II , P < .05). These findings indicate that blockade of bradykinin B-2-re ceptors enhances the slow presser effect induced by moderate to severe increases in circulating Ang II levels. Therefore, endogenous kinins may play a role in preventing the chronic pressure effect of an excess of Ang II.