title: Modulation of angiotensin-converting enzyme by nitric oxide.
abstract: 1. The aim of the present study was to determine the effect of nitric oxide (NO) on angiotensin-converting enzyme (ACE) activity. 2. A biochemical study was performed in order to analyse the effect of the NO-donors, SIN-1 and diethylamine/NO (DEA/NO), and of an aqueous solution of nitric oxide on the ACE activity in plasma from 3-month old male Sprague-Dawley rats and on ACE purified from rabbit lung. SIN-1 significantly inhibited the activity of both enzymes in a concentration-dependent way between 1 and 100 microM. DEA/NO inhibited the activity of purified ACE from 0.1 microM to 10 microM and plasma ACE, with a lower potency, between 1 and 100 microM. An aqueous solution of NO (100 and 150 microM) also inhibited significantly the activity of both enzymes. Lineweaver-Burk plots indicated an apparent competitive inhibition of Hip-His-Leu hydrolysis by NO-donors. 3. Modulation of ACE activity by NO was also assessed in the rat carotid artery by comparing contractions elicited by angiotensin I (AI) and AII. Concentration-response curves to both peptides were performed in arteries with endothelium in the presence of the guanylyl cyclase inhibitor, ODQ (10 microM), and the inhibitor of NO formation, L-NAME (0.1 mM). NO, which is still released from endothelium in the presence of 10 microM ODQ, elicited a significant inhibition of AI contractions at low concentrations (1 and 5 nM). In the absence of endothelium, 1 microM SIN-1 plus 10 microM ODQ, as well as 10 microM DEA/NO plus 10 microM ODQ induced a significant inhibition on AI-induced contractions at 1 and 5 nM and at 1-100 nM, respectively. 4. In conclusion, we demonstrated that (i) NO and NO-releasing compounds inhibit ACE activity in a concentration-dependent and competitive way and that (ii) NO release from endothelium physiologically reduces conversion of AI to AII.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ackermann
authors.forename: M S
authors.initials: MS
authors.lastname: Fernández-Alfonso
authors.forename: R
authors.initials: R
authors.lastname: Sánchez de Rojas
authors.forename: T
authors.initials: T
authors.lastname: Ortega
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: C
authors.initials: C
authors.lastname: González
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000201:enzymology; D004048:Diethylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000097:blood / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000806:Angiotensin-Converting Enzyme Inhibitors; D004048:Diethylamines; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010069:Oxadiazoles; D011810:Quinoxalines; D000804:Angiotensin II; C010980:hippuryl-histidyl-leucine; D009569:Nitric Oxide; C002385:linsidomine; D000803:Angiotensin I; C034281:diethylamine; D008981:Molsidomine; D007703:Peptidyl-Dipeptidase A; D006162:Guanylate Cyclase