Chronic inhibition of bradykinin B₂-receptors enhances the slow vasopressor response to angiotensin II

The contribution of endogenous kinins in the regulation of blood pressure of angiotensin-treated rats was evaluated using the new bradykinin B₂- receptor antagonist Hoe 140 (D-Arg,[Hyp³, Thi⁵, D-Tic⁷, Oic⁸]- bradykinin). Chronic infusion of Hoe 140 at 75 nmol/d (a dose able to inhibit the vasodepressor effect of an intra-aortic bolus injection of 0.85 nmol/kg bradykinin) did not alter systolic blood pressure (tail-cuff plethysmography). Chronic infusion of angiotensin II (Ang II) induced a dose- related increase in systolic blood pressure and plasma Ang II levels. The vasopressor effect of 40 or 100 nmol/d Ang II was enhanced in rats given chronic infusion of Hoe 140 (by 12 and 14 mm Hg, respectively), whereas the increase in plasma Ang II levels remained unaltered. Furthermore, a low nonpressor dose of Ang II (20 nmol/d) was then able to increase blood pressure during chronic blockade of bradykinin receptors by Hoe 140 (from 126±3 to 137±3 mm Hg, P2-receptors enhances the slow pressor 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.