Chu A, Chambers D E, Lin C C, Kuehl W D, Palmer R M, Moncada S, Cobb F R
Department of Medicine, Duke Medical Center, Durham, North Carolina.
J Clin Invest. 1991 Jun;87(6):1964-8. doi: 10.1172/JCI115223.
The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses greater than or equal to 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular end-diastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest does of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholine-stimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions.
通过使用一氧化氮生成的特异性抑制剂 NG-单甲基-L-精氨酸（L-NMMA）抑制内源性一氧化氮生成，研究了一氧化氮在长期植入仪器的清醒犬冠状动脉基础血管运动张力和刺激的内皮依赖性舒张中的作用。在四只清醒犬中，将冠状动脉尺寸晶体长期植入回旋动脉以测量心外膜冠状动脉直径，并植入多普勒血流探头以定量阶段性冠状动脉血流（远端调节性阻力血管的血管运动）。在给予 5、15、50 和 120 mg/kg 的 L-NMMA 之前和之后，记录基础心外膜冠状动脉直径、乙酰胆碱刺激的内皮依赖性舒张、心外膜动脉的血流诱导的内皮依赖性舒张和阶段性血流。L-NMMA 引起基础心外膜冠状动脉血管运动张力剂量相关的增加。同时主动脉压升高，心率降低。在剂量大于或等于 50 mg/kg 时，静息阶段性冠状动脉血流也减少。左心室舒张末期压力和收缩力无明显变化。相比之下，仅在输注最高剂量的 L-NMMA（120 mg/kg）后，血流诱导或乙酰胆碱刺激的内皮依赖性反应才减弱。在存在 L-精氨酸（660 mg/kg）的情况下，基础血管运动张力和乙酰胆碱刺激的内皮依赖性反应的变化恢复到对照状态。这些数据支持这样的观点，即一氧化氮在调节基础血管运动以及由乙酰胆碱刺激或心外膜冠状动脉血流增加引起的内皮依赖性舒张中起重要作用，并且在生理条件下也影响冠状动脉血流的调节。
