title: Chronic angiotensin-converting enzyme inhibition and endothelial function of rat aorta.
abstract: To determine whether chronic angiotensin-converting enzyme (ACE) inhibition produces functional changes in the aorta normotensive rats, four groups of rats were studied in parallel for 6 weeks. Group 1 orally received ramipril and beta 2-kinin antagonist HOE140 500 micrograms/kg per day s.c. by injection for the remaining 2 weeks; group 3, hydralazine 100 mg/kg per day PO for 6 weeks; group 4 (control), subcutaneous injections of saline solution during the last 2 of 6 weeks. In aorta isolated from group 1 the relaxations induced by bradykinin, acetylcholine, and histamine were significantly potentiated compared with those of group 4. In group 3, despite a decrease in systolic blood pressure similar to that induced by ramipril treatment, the responses to these three endothelium-dependent vasodilators were not different from those of group 4. In group 2, bradykinin-induced relaxations were completely abolished whereas acetylcholine-induced and histamine-induced relaxations were to those of group 4. The inhibitory effect of the endothelium on serotonin-induced contractions was significantly increased in preparations of group 1 compared with those of groups 2 through 4. Indirect measurements of nitric oxide formation such as contractions evoked by NG-monomethyl-L-arginine (L-NMMA) and aortic cGMP content were also significantly enhanced in preparations from group 1 compared with those of groups 2 through 4. Moreover, because the relaxations to nitroglycerin and nitroprusside were similar in groups 1, 2, and 4 an alteration of the guanylate cyclase activity by ramipril treatment is quite unlikely. Thus long-term treatment with ramipril potentiates the endothelium-dependent responses in the rat aorta by enhancing nitric oxide availability.
authors.affiliation: Department of Cardiology, Erasme Hospital, Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Berkenboom
authors.forename: D
authors.initials: D
authors.lastname: Brékine
authors.forename: P
authors.initials: P
authors.lastname: Unger
authors.forename: K
authors.initials: K
authors.lastname: Grosfils
authors.forename: M
authors.initials: M
authors.lastname: Staroukine
authors.forename: J
authors.initials: J
authors.lastname: Fontaine
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000032:analysis; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D006830:Hydralazine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065679:icatibant; D001120:Arginine; D007703:Peptidyl-Dipeptidase A; D006152:Cyclic GMP; D017257:Ramipril; D001920:Bradykinin