Possible mechanism of captopril induced endothelium-dependent relaxation in isolated rabbit aorta.
The mechanism of captopril, an angiotensin converting enzyme (ACE) inhibitor with sulfhydryl group (SH) in its structure, to produce an endothelium-dependent vasorelaxation was studied. In rabbit aorta with intact endothelium and precontracted with phenylephrine, captopril and superoxide dismutase (SOD) produced dose-dependent relaxation. Lisinopril, an ACE inhibitor without a -SH group in its structure, did not produce endothelium-dependent relaxation. It was observed that captopril, like SOD, produced the relaxation by protecting the EDRF from getting inactivated by superoxide anions as pyrogallol and methylene blue inhibited both the captopril and SOD-mediated relaxation. The free radical scavenging action of captopril is further substantiated by the observation that captopril, but not lisinopril, inhibited FeCl3/ascorbic acid-induced lipid peroxidation in whole tissue homogenates of rabbit aorta to a level comparable to that of SOD. These results suggest that endothelium-dependent vasodilation produced by captopril may be due to its ability to scavenge superoxide anion and this property may be ascribed to the -SH group present in its structure.
Mittra
S
S
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Singh
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D010656:Phenylephrine; D002216:Captopril; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; C024555:ferric chloride