Van Winkle D M, Feigl E O
Department of Physiology and Biophysics, University of Washington Medical School, Seattle 98195.
Circ Res. 1989 Dec;65(6):1580-93. doi: 10.1161/01.res.65.6.1580.
Intracoronary administration of acetylcholine or efferent vagal stimulation causes coronary vasodilation in dogs. However, in baboons it has been reported that intracoronary acetylcholine results in a fall in coronary blood flow and that stimulation of the vagi is without effect. The dose response of intracoronary acetylcholine and the effect of efferent vagal stimulation on the coronary circulation were reinvestigated in closed-chest, anesthetized dogs and baboons. The left main coronary artery was cannulated and perfused at constant pressure. alpha-Adrenergic and beta-adrenergic receptors were pharmacologically blocked with phenoxybenzamine and propranolol. Heart rate was held constant by right ventricular pacing. In dogs, intracoronary infusion of acetylcholine (1-300 micrograms/min) elicited a dose-dependent increase in steady-state coronary blood flow and coronary sinus oxygen tension, without a change in myocardial oxygen consumption. Vagal stimulation caused a coronary vasodilation that was attenuated by a metabolically mediated decrease in flow. In baboons, acetylcholine increased steady-state coronary blood flow in the dose range of 1-10 micrograms/min, caused little change at 30 micrograms/min, and decreased flow at 100-300 micrograms/min. Coronary sinus oxygen tension increased in a dose-dependent manner up to 10 micrograms/min. Myocardial oxygen consumption was unchanged in the dose range of 1-10 micrograms/min and declined between 30 and 300 micrograms/min. Efferent stimulation of the vagi resulted in coronary dilation obscured by a metabolic reduction of flow. It is concluded that 1) low doses of acetylcholine elicit a primary coronary vasodilation in both species, but in baboons high doses of acetylcholine cause a reduction of both myocardial oxygen consumption and coronary blood flow below control values and 2) vagal stimulation causes a competition between coronary vasodilation and metabolic reduction of flow in dogs and baboons.
冠状动脉内注射乙酰胆碱或传出迷走神经刺激可使犬的冠状动脉扩张。然而，据报道，在狒狒中，冠状动脉内注射乙酰胆碱会导致冠状动脉血流量下降，而刺激迷走神经则无作用。我们在开胸麻醉的犬和狒狒中重新研究了冠状动脉内注射乙酰胆碱的剂量反应以及传出迷走神经刺激对冠状动脉循环的影响。将左冠状动脉主干插管并在恒压下灌注。用酚苄明和普萘洛尔药理学阻断α-肾上腺素能和β-肾上腺素能受体。通过右心室起搏使心率保持恒定。在犬中，冠状动脉内输注乙酰胆碱（1 - 300微克/分钟）可引起稳态冠状动脉血流量和冠状窦氧张力呈剂量依赖性增加，而心肌耗氧量无变化。迷走神经刺激引起冠状动脉扩张，但因代谢介导的血流减少而减弱。在狒狒中，乙酰胆碱在1 - 10微克/分钟的剂量范围内增加稳态冠状动脉血流量，在30微克/分钟时变化不大，在100 - 300微克/分钟时血流量减少。冠状窦氧张力在10微克/分钟以下呈剂量依赖性增加。在1 - 10微克/分钟的剂量范围内心肌耗氧量无变化，在30 - 300微克/分钟之间下降。传出迷走神经刺激导致冠状动脉扩张，但被代谢性血流减少所掩盖。结论是：1）低剂量的乙酰胆碱在两种动物中均引起原发性冠状动脉扩张，但在狒狒中，高剂量的乙酰胆碱会导致心肌耗氧量和冠状动脉血流量均降至对照值以下；2）迷走神经刺激在犬和狒狒中导致冠状动脉扩张与代谢性血流减少之间存在竞争。
