Effects of teprotide, captopril and enalaprilat on arterial wall kininase and angiotensin converting activity.
We have previously shown that the hypotensive action of angiotensin I (ANG I) converting enzyme (ACE) inhibitors is temporally related to a long-lasting inhibition of kininase activity in the arterial wall. More recently, we showed that conversion of ANG I in the perfused mesenteric vascular bed was not inhibited by enalaprilat at concentrations above those which maximally inhibited kininase activity. The present study extends these observations to two other ACE inhibitors and to another vascular bed, the rat hindlimb preparation. Like enalaprilat, captopril (0.06-1.5 mumol/l) or teprotide (0.4-10 mumol/l) did not inhibit the conversion of ANG I in the perfused mesenteric bed, although the response to bradykinin was substantially potentiated, indicating that the ACE inhibitor decreased kininase activity. In the perfused hindlimb preparations, enalaprilat reduced kininase activity without altering the conversion of ANG I. Enalaprilat or captopril administered to rats caused a decrease in mean arterial blood pressure that lasted for over 24 h. In mesenteric preparations taken from animals 24 h after treatment with ACE inhibitors, kininase activity was inhibited whereas converting activity was unchanged. Therefore, the long-lasting hypotensive effect of ACE inhibition is apparently related to a prolonged inhibition of kininase activity in the arterial wall, which is believed to be the target for ACE inhibitor activity.
Lindsey
C J
CJ
Department of Biophysics, Escola Paulista de Medicina São Paulo, SP, Brazil.
Bendhack
L M
LM
Paiva
A C
AC
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D013722:Teprotide; D015773:Enalaprilat; D001920:Bradykinin