CHRONIC INHIBITION OF BRADYKININ RECEPTORS ALTERS CARDIOVASCULAR FUNCTION IN RATS WITH AN EXCESS OF CIRCULATING VASOCONSTRICTORS

1. The contribution of endogenous kinins to the regulation of blood pr essure of angiotensin-treated rats was evaluated using the new bradyki nin B-2-receptor antagonist Hoe 140 (D-Arg [Hyp(3),Thi(5),D-Tic(7),Oic (8)]-bradykinin). 2. Chronic intraperitoneal infusion of 20 nmol/day a ngiotensin II did not alter systolic blood pressure or plasma angioten sin II levels. A significant increase in plasma aldosterone and cortic osterone levels was observed after 4 weeks (from 89 +/- 20 to 140 +/- 22 and from 147 +/- 30 to 225 +/- 33 pg/ml, respectively; P<0.05). 3. Combined administration of 20 nmol/day angiotensin II and 75 nmol Hoe 140 induced a significant increase in systolic blood pressure from 126 +/- 3 to 142 +/- 3 and 137 +/- 3 mmHg, at 1 and 4 weeks, respectively (P<0.05). This effect was not accompanied by significant changes in p lasma angiotensin II concentration. The angiotensin-induced increase i n plasma levels of aldosterone and corticosterone was not altered by t he antagonist Hoe 140. 4. These findings indicate that blockade of end ogenous kinin receptors enhances the slow presser effect induced by an giotensin II. Therefore, endogenous kinins may play a role in preventi ng the cardiovascular effects of an excess of vasoconstrictors.