Relaxation of isolated coronary arteries by angiotensin-converting enzyme inhibitors: role of endothelium-derived kinins.
In the presence of indomethacin (10 microM) and without previous exposure to bradykinin, two angiotensin-converting enzyme (ACE) inhibitors, moexiprilat and ramiprilat (0.1 microM), elicited distinct relaxation responses from preconstricted endothelium-intact but not from denuded bovine coronary artery rings, and enhanced the relaxation response to bradykinin (3 nM). All of these responses were strongly reduced by the selective B2-kinin receptor antagonist Hoe 140 (0.1 microM). Bradykinin (30 nM), moexiprilat or ramiprilat (0.3 microM) also significantly increased the cyclic GMP content of these coronary segments, an effect which was abolished by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA; 30 microM) or by removal of the endothelium. L-NNA also strongly reduced the relaxation response to moexiprilat but only partially inhibited that to bradykinin, demonstrating that the ACE inhibitor-induced relaxation was predominantly mediated by endothelial NO release, whereas bradykinin acted in part through another endothelium-dependent mechanism. These findings suggest that ACE inhibitors induce endothelium-dependent relaxation presumably by facilitating the accumulation of endothelium-derived vasoactive kinins in or at the vessel wall. This local mechanism may significantly contribute to the dilator action of these compounds in vivo.
Hecker
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M
Department of Applied Physiology, University of Freiburg, FRG.
Bara
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Busse
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007705:Kinins / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D013552:Swine; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D007705:Kinins; D044005:Tetrahydroisoquinolines; C052549:ramiprilat; D006152:Cyclic GMP; C059506:moexiprilat; D017257:Ramipril; D001920:Bradykinin