ACE-inhibition, kinins, and vascular PGI2 synthesis.
In the present studies, ex vivo-, in vitro-, and in vivo-effects of three structurally different angiotensin I-converting enzyme (ACE) inhibitors on the kallikrein-kinin and eicosanoid systems are described. In the ex vivo- and in vitro-experiments using isolated rat aorta, vascular prostacyclin (PGI2) production is dose-dependently stimulated by the ACE inhibitors captopril, lisinopril, and ramipril. Furthermore, the ACE inhibitor-induced augmentation of vascular PGI2 synthesis observed in vitro was completely inhibited by the competitive bradykinin antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin suggesting that ACE inhibitors stimulate PGI2 generation by an enhancement of kinin activity. In the in vivo studies in healthy volunteers, we used platelet cyclic adenosine-5'-monophosphate (cAMP) and cyclic guanosine-5'-monophosphate (cGMP) as indirect parameters of the activity of prostacyclin and the endothelium-derived relaxing factor, respectively. Since platelet cAMP and cGMP were unaffected by an acute dose of 10 mg of lisinopril, our data do not support the concept that the interference of ACE inhibitors with the kallikrein-kinin-prostaglandin system observed ex vivo and in vitro participates in the haemodynamic effects of these agents in humans in vivo.
Hoffmann
G
G
Medizinische Universitäts-Poliklinik, Bonn 1, FRG.
Düsing
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004151:Dipeptides / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000378:metabolism*; D017706:Lisinopril; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007705:Kinins; D002216:Captopril; D011464:Epoprostenol; D000242:Cyclic AMP; D017706:Lisinopril; D007610:Kallikreins; D006152:Cyclic GMP; D017257:Ramipril