title: Role of nitric oxide in vascular tone and in reactivity to isoproterenol and adenosine in the goat coronary circulation.
abstract: The present study examined the role of nitric oxide in coronary vascular tone and in the coronary vasodilatation in response to beta-adrenoceptor stimulation and adenosine. In anesthetized goats, the effects of intracoronary and i.v. administration of the inhibitor of nitric oxide synthesis, N(w)-nitro-L-arginine methyl ester (L-NAME), and those of isoproterenol, adenosine and acetylcholine on coronary blood flow, measured electromagnetically in the left circumflex coronary artery, were recorded. Intracoronary infusion of L-NAME (30-40 microg kg(-1) min(-1), four goats) reduced resting coronary blood flow by 14+/-3% (P<0.05) without changing arterial pressure and heart rate. L-NAME (40 mg kg(-1), eight goats) i.v. reduced resting coronary blood flow by 19+/-4% (P<0.05), increased mean systemic arterial pressure by 22+/-3% (P<0.01) and decreased heart rate by 10+/-2% (P<0.05). These effects of L-NAME were partially, but significantly reversed by L-arginine (six goats). Isoproterenol (10-100 ng, eight goats), adenosine (0.3-10 microg, seven goats) and acetylcholine (3-100 ng, five goats), injected intracoronarily, increased coronary conductance in a dose-dependent way and, under control conditions, these increases for isoproterenol, ranged from 32+/-5% to 82+/-12%; for adenosine, 6+/-2% to 174+/-22%; and for acetylcholine, 39+/-5% to 145+/-15%. During i.v. L-NAME the increases in coronary conductance induced by isoproterenol and acetylcholine were significantly reduced by about 50 and 60% (P<0.05), respectively, whereas those induced by adenosine were significantly increased further (about 30-100%, P<0. 05). During L-NAME plus L-arginine, the effects of isoproterenol, acetylcholine and adenosine on coronary conductance were not significantly different from those under control conditions. Therefore, it is suggested that in the coronary circulation: (a) nitric oxide may produce a basal vasodilator tone under normal conditions; (b) nitric oxide may be an intermediate in the vasodilatation due to beta-adrenoceptor stimulation and acetylcholine, and (c) the vasodilatation due to adenosine is potentiated during reduction of nitric oxide production.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 2, 28029, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Fernández
authors.forename: M A
authors.initials: MA
authors.lastname: Sánchez
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.forename: A L
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: L
authors.initials: L
authors.lastname: Monge
authors.forename: B
authors.initials: B
authors.lastname: Gómez
authors.forename: G
authors.initials: G
authors.lastname: Diéguez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006041:Goats; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D000241:Adenosine; D007545:Isoproterenol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester