EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME AND NEUTRAL ENDOPEPTIDASE INHIBITORS - INFLUENCE OF BRADYKININ

These experiments compare the effects of a neutral endopeptidase inhib itor, retrothiorphan, mercaptomethyl-2-phenyl)ethyl]amino-1-oxopropano ic acid, a converting enzyme inhibitor, enalaprilat, and the combinati on of the two inhibitors on changes in blood pressure and renal functi on induced by exogenous and endogenous bradykinin in deoxycorticostero ne acetate (DOCA)-salt rats. Enalaprilat potentiated the exogenous bra dykinin-induced hypotensive responses while retrothiorphan potentiated the effects on urinary cyclic-GMP (cGMP) and bradykinin. The combinat ion potentiated the exogenous bradykinin-induced hypotensive effects a nd the bradykinin-induced urinary excretion of cGMP, bradykinin and pr ostaglandin. The bradykinin B-2 receptor antagonist, Hoe 140, had no e ffect on the enalaprilat- and retrothiorphan-induced changes in blood pressure and renal function. In conclusion, while angiotensin-converti ng enzyme and neutral endopeptidase are involved in the vascular and r enal catabolism of exogenous bradykinin, the effects of the peptidase inhibitors do not appear to depend on the protection of endogenous bra dykinin under acute conditions in DOCA-salt rats.