title: Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in canine femoral arteries.
abstract: The effects of angiotensin-converting enzyme (ACE) inhibitors on vascular reactivity were investigated using isolated canine femoral arteries with and without endothelium. N-N-(S)-1-carboxy-3-phenylpropyl-L-alanyl-N-(indan-2-yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl ACE inhibitor) and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10(-5) M) relaxed in a dose-dependent manner canine femoral arterial rings precontracted with prostaglandin F2 alpha in the presence of endothelium only. The endothelium-dependent relaxations by M-1 and captopril were completely blocked by methylene blue, an inhibitor of soluble guanylate cyclase; NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis; and oxyhemoglobin, an inactivator of nitric oxide; they were partially blocked by aspirin, an inhibitor of cyclooxygenase and were enhanced by superoxide dismutase, a radical scavenger. The inhibitory effect of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of L-arginine. Moreover, a bradykinin antagonist partially inhibited these relaxations. These results suggest that endothelium-dependent relaxations by M-1 and captopril in canine femoral arteries are mediated through the release of both prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.
authors.affiliation: Third Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Moroi
authors.forename: N
authors.initials: N
authors.lastname: Akatsuka
authors.forename: M
authors.initials: M
authors.lastname: Fukazawa
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: J
authors.initials: J
authors.lastname: Aikawa
authors.forename: A
authors.initials: A
authors.lastname: Namiki
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007189:Indans; D010108:Oxyhemoglobins; D019323:omega-N-Methylarginine; C086460:N-(N-(1-carboxy-3-phenylpropyl)alanyl)-N-(indan-2-yl)glycine; D001120:Arginine; D002216:Captopril; D015237:Dinoprost; D013482:Superoxide Dismutase; D001241:Aspirin; D008751:Methylene Blue