Effects of angiotensin-converting enzyme and neutral endopeptidase inhibitors: influence of bradykinin.
These experiments compare the effects of a neutral endopeptidase inhibitor, retrothiorphan, 1-[(1-mercaptomethyl-2-phenyl)ethyl]amino-1-oxopropanoic acid, a converting enzyme inhibitor, enalaprilat, and the combination of the two inhibitors on changes in blood pressure and renal function induced by exogenous and endogenous bradykinin in deoxycorticosterone acetate (DOCA)-salt rats. Enalaprilat potentiated the exogenous bradykinin-induced hypotensive responses while retrothiorphan potentiated the effects on urinary cyclic-GMP (cGMP) and bradykinin. The combination potentiated the exogenous bradykinin-induced hypotensive effects and the bradykinin-induced urinary excretion of cGMP, bradykinin and prostaglandin. The bradykinin B2 receptor antagonist, Hoe 140, had no effect on the enalaprilat- and retrothiorphan-induced changes in blood pressure and renal function. In conclusion, while angiotensin-converting enzyme and neutral endopeptidase are involved in the vascular and renal catabolism of exogenous bradykinin, the effects of the peptidase inhibitors do not appear to depend on the protection of endogenous bradykinin under acute conditions in DOCA-salt rats.
Pham
I
I
INSERM U 367, Paris, France.
Gonzalez
W
W
Doucet
J
J
Fournie-Zaluski
M C
MC
Roques
B P
BP
Michel
J B
JB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D015773:Enalaprilat / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D015244:Thiorphan / Q000031:analogs & derivatives / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; C065679:icatibant; C072559:retrothiorphan; D015244:Thiorphan; D015260:Neprilysin; D015773:Enalaprilat; D006152:Cyclic GMP; D001920:Bradykinin