title: Chronic ouabain treatment increases the contribution of nitric oxide to endothelium-dependent relaxation.
abstract: The aim of this study was to analyze the contribution of nitric oxide, prostacyclin and endothelium-dependent hyperpolarizing factor to endothelium-dependent vasodilation induced by acetylcholine in rat aorta from control and ouabain-induced hypertensive rats. Preincubation with the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl esther (L-NAME) inhibited the vasodilator response to acetylcholine in segments from both groups but to a greater extent in segments from ouabain-treated rats. Basal and acetylcholine-induced nitric oxide release were higher in segments from ouabain-treated rats. Preincubation with the prostacyclin synthesis inhibitor tranylcypromine or with the cyclooxygenase inhibitor indomethacin inhibited the vasodilator response to acetylcholine in aortic segments from both groups. The Ca2+-dependent potassium channel blocker charybdotoxin inhibited the vasodilator response to acetylcholine only in segments from control rats. These results indicate that hypertension induced by chronic ouabain treatment is accompanied by increased endothelial nitric oxide participation and impaired endothelium-dependent hyperpolarizing factor contribution in acetylcholine-induced relaxation. These effects might explain the lack of effect of ouabain treatment on acetylcholine responses in rat aorta.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Aras-López
authors.forename: J
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: R
authors.initials: R
authors.lastname: Hernanz
authors.forename: A M
authors.initials: AM
authors.lastname: Briones
authors.forename: L V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.forename: G
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014191:Tranylcypromine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D014665:Vasodilator Agents; D018999:Charybdotoxin; D009569:Nitric Oxide; D014191:Tranylcypromine; D010042:Ouabain; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin