Angiotensin-converting enzyme inhibitors unmask endogenous kinin production by bovine coronary artery endothelium.
The angiotensin converting enzyme (ACE) inhibitors, moexiprilat and ramiprilat, relaxed preconstricted endothelium-intact bovine coronary artery rings and enhanced the relaxant response to bradykinin. The relaxation was observed in the presence of a cyclooxygenase inhibitor and without previous exposure to bradykinin. ACE inhibitor-dependent relaxation was attenuated by the selective B2-kinin receptor antagonist, Hoe 140, and completely abolished by removal of the endothelium. Bradykinin or moexiprilat also significantly increased the cyclic guanosine monophosphate (cGMP) content of these coronary segments, an effect which was abolished by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (NNA), or by removal of the endothelium. NNA also diminished the relaxant response to moexiprilat, but only partially inhibited that to bradykinin, suggesting that the ACE inhibitor-induced relaxation was predominantly mediated by endothelial NO release, whereas bradykinin acted in part by another endothelium-dependent mechanism. These findings indicate that ACE inhibitors can elicit endothelium-dependent relaxations presumably by facilitating the accumulation of endothelium-derived kinins in or at the vessel wall. This local mechanism may significantly contribute to the antihypertensive action of these compounds in vivo.
Hecker
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M
Department of Applied Physiology, University of Freiburg, Germany.
Bara
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Busse
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002417:Cattle; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D019335:Nitroarginine; D009569:Nitric Oxide; C052549:ramiprilat; C065679:icatibant; D001120:Arginine; D006152:Cyclic GMP; C059506:moexiprilat; D017257:Ramipril; D001920:Bradykinin