Role of nitric oxide in vascular tone and in reactivity to isoproterenol and adenosine in the goat coronary circulation.
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.
Fernández
N
N
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 2, 28029, Madrid, Spain.
Sánchez
M A
MA
Martínez
M A
MA
García-Villalón
A L
AL
Monge
L
L
Gómez
B
B
Diéguez
G
G
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
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