Vascular catabolism of bradykinin in the isolated perfused rat kidney

Kinins in the circulation are rapidly metabolized by several different pept idases. The purpose of this study was to evaluate the contribution of membr ane-bound peptidases to kinin metabolism in the renal circulation. Experime nts were performed in vitro, in isolated rat kidneys perfused at a constant flow rate (8 ml/min) with Tyrode's solution. The effects of peptidase inhi bitors were evaluated on the functional vasodilator response caused by brad ykinin (30 nM) or [Tyr(Me)(8)]bradykinin (10 nM) via activation of bradykin in B-2 receptors in kidneys precontracted with prostaglandin F-2 alpha. Ang iotensin converting enzyme inhibitors, enalaprilat (3 muM), ramiprilat (1 m uM) or lisinopril (1 muM), increased the bradykinin-induced renal vasodilat ion by 40% or more. Inhibitors of neutral endopeptidase (thiorphan or phosp horamidon, 10 muM), basic carboxypeptidase (DL-2-mercaptomethyl-3-guanidino -ethylthiopropanoic acid or MGTPA, 10 muM) and aminopeptidase P (apstatin, 20 muM) however did not enhance the renal vasodilator response elicited by kinins, whatever tested alone or in the presence of lisinopril. These findi ngs indicate that angiotensin converting enzyme is the major peptidase whos e inhibition potentiates the renal bradykinin B-2 receptor mediated vasodil ator response of kinins. The relative contribution in this potentiation of inhibition of kinin inactivation and of cross-talk of angiotensin convertin g enzyme with bradykinin B-2 receptor remains however to be clarified. (C) 2000 Elsevier Science B.V. All rights reserved.