Fernández N, Sánchez M A, Martínez M A, García-Villalón A L, Monge L, Gómez B, Diéguez G
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 2, 28029, Madrid, Spain.
Eur J Pharmacol. 2000 Jan 3;387(1):93-9. doi: 10.1016/s0014-2999(99)00766-9.
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.
本研究探讨了一氧化氮在冠状动脉张力以及对β-肾上腺素能受体刺激和腺苷反应的冠状动脉血管舒张中的作用。在麻醉的山羊中，记录了冠状动脉内和静脉注射一氧化氮合成抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）以及异丙肾上腺素、腺苷和乙酰胆碱对左旋冠状动脉中通过电磁法测量的冠状动脉血流量的影响。冠状动脉内输注L-NAME（30 - 40μg kg⁻¹ min⁻¹，4只山羊）使静息冠状动脉血流量降低14±3%（P<0.05），而动脉血压和心率未改变。静脉注射L-NAME（40 mg kg⁻¹，8只山羊）使静息冠状动脉血流量降低19±4%（P<0.05），使平均体动脉压升高22±3%（P<0.01），使心率降低10±2%（P<0.05）。L-精氨酸（6只山羊）部分但显著地逆转了L-NAME的这些作用。冠状动脉内注射异丙肾上腺素（10 - 100 ng，8只山羊）、腺苷（0.3 - 10μg，7只山羊）和乙酰胆碱（3 - 100 ng，5只山羊）以剂量依赖的方式增加冠状动脉传导性，在对照条件下，异丙肾上腺素引起的增加范围为32±5%至82±12%；腺苷为6±2%至174±22%；乙酰胆碱为39±5%至145±15%。在静脉注射L-NAME期间，异丙肾上腺素和乙酰胆碱诱导的冠状动脉传导性增加分别显著降低约50%和60%（P<0.05），而腺苷诱导的增加则进一步显著增加（约30 - 100%，P<0.05）。在L-NAME加L-精氨酸期间，异丙肾上腺素、乙酰胆碱和腺苷对冠状动脉传导性的影响与对照条件下无显著差异。因此，提示在冠状动脉循环中：（a）一氧化氮在正常情况下可能产生基础血管舒张张力；（b）一氧化氮可能是β-肾上腺素能受体刺激和乙酰胆碱引起血管舒张的中间介质；（c）在一氧化氮生成减少期间，腺苷引起的血管舒张增强。
