RENAL VASCULAR-RESPONSES OF KININS IN THE ISOLATED-PERFUSED RAT-KIDNEY

Kinins, by an autocrine or paracrine hormonal action, are potent modul ators of regional vasomotricity. Their effects on the renal circulatio n are not well defined. The aim of this study was to analyse the renal vascular response induced by bradykinin, to precise the type(s) of re ceptor involved and to evaluate the contribution of various peptidases in the local catabolism of the kinin. Experiments were performed on t he isolated rat kidney, perfused in an open circuit, at a constant flo w of 8 mL/min, with a Tyrode's solution. Vasodilator responses were ev aluated after renal vascular tone had been restored by a continuous pe rfusion with prostaglandin F-2 alpha, Infusion of bradykinin (0.1-30 n M) induced a concentration-dependent renal vasorelaxation. A maximal r esponse of 39.5 +/- 2.8 % (n = 32) reversion of the tone induced by pr ostaglandin F-2 alpha (about SO % of the maximal response induced by a cetylcholine on the same kidneys) was obtained at 30 nM. Bradykinin-in duced vasodilatation was completely inhibited by HOE 140 (10() nM), a selective bradykinin B-2 receptor antagonist. At a supramaximal concen tration of 300 nM, bradykinin-induced vasorelaxation was modulated by a concomitant vasoconstriction. A concentration-dependent vasoconstric tion was also obtained with desArg(9)bradykinin (1-8 mu M), a selectiv e agonist of the bradykinin B-1 receptor. The inhibition of neutral en dopeptidase by phosphoramidon (10 mu M) or the inhibition of carboxype ptidase M by MGTPA (10 mu M) did not modify the bradykinin-induced ren al vasorelaxation. On the other hand, the inhibition of angiotensin I converting enzyme by lisinopril (1 mu M) potentiated by about 32 % the vasorelaxant response Induced by 30 nM bradykinin (52.3 +/- 11.8 % re laxation, n = 5, p < 0.05). Present results demonstrate that 1) bradyk inin primarily evokes B-2 receptor-linked renal vasodilatation, 2) bra dykinin B-1 receptors appear also to be present on the rat renal vascu lature and 3) angiotensin I converting enzyme contributes to the local vascular catabolism of the kinin.