Jones C J, Kuo L, Davis M J, Chilian W M
University of Wales College of Medicine, Cardiff, United Kingdom.
Am J Physiol. 1996 Aug;271(2 Pt 2):H461-8. doi: 10.1152/ajpheart.1996.271.2.H461.
The actions of nitroglycerin on the coronary microcirculation are controversial, with some laboratories reporting that coronary arterioles dilate to the drug and others reporting that they do not. Our goal was to reconcile these disparate observations. Specifically, we hypothesized that dilation of coronary arterioles by nitroglycerin is overwhelmed by intrinsic autoregulatory escape mechanisms. Accordingly, we projected that coronary arterioles would show transient, but not sustained, dilation to nitroglycerin in vivo. Furthermore, we hypothesized that isolated coronary arterioles would show sustained dilation to the drug, because intrinsic escape mechanisms would be absent under these conditions. To test these hypotheses, we measured diameter changes of canine coronary microvessels in vivo during continuous nitroglycerin administration (intracoronary infusion or epicardial suffusion) using intravital fluorescent microscopy (n = 17 dogs) at two time points: early (1-3 min), when coronary artery blood flow velocity was increased, and late (15-20 min), after blood flow velocity returned to control. Tb study responses of coronary arterioles in the absence of autoregulatory influences, we measured the diameter of isolated canine coronary arterioles to varying doses of nitroglycerin (n = 8 vessels, maximal diameter 81 +/- 4 microns). During the early phase of nitroglycerin infusion (1,3, and 10 micrograms.kg-1.min-1), coronary arterioles dilated by 4 +/- 1, 7 +/- 2, and 13 +/- 2% (all P < 0.05), whereas small arteries dilated by 1 +/- 2, 3 +/- 1, and 4 +/- 1%, respectively (P < 0.05 for the higher doses). Coronary artery blood velocity measured increased by 45 +/- 15% (3 micrograms.kg-1.min-1, P < 0.05). Suffusion of nitroglycerin (10(-5) M) dilated coronary arterioles, but not small arteries, by 17 +/- 5% (P < 0.05) between 1 and 3 min. After 15-20 min of nitroglycerin (3 micrograms.kg-1.min-1 by intracoronary infusion), diameters of coronary arterioles and coronary artery blood velocity returned to control, whereas dilation of small arteries remained significant at 4 +/- 1%. Coronary arteriolar dilation by epicardial suffusion of nitroglycerin also waned to control values by 15-20 min, whereas dilation of small arteries was observed: 5 +/- 2% (P < 0.05). In vitro, nitroglycerin caused dose-dependent dilation of coronary arterioles to their maximal diameter, which was sustained for 20 min. Thus nitroglycerin dilates coronary arterioles and small arteries. The dilation in vivo is transient for arterioles but sustained for arteries. In vitro, the dilation is sustained. Because microvessels in vitro are capable of sustaining dilation for 20 min, we conclude that the waning of arteriolar dilation in vivo is related to autoregulatory escape from dilation by nitroglycerin.
硝酸甘油对冠状动脉微循环的作用存在争议，一些实验室报告冠状动脉小动脉会对该药物产生扩张反应，而另一些实验室则报告不会。我们的目标是调和这些不同的观察结果。具体而言，我们假设硝酸甘油引起的冠状动脉小动脉扩张被内在的自动调节逃逸机制所抵消。因此，我们推测冠状动脉小动脉在体内会对硝酸甘油表现出短暂但非持续性的扩张。此外，我们假设分离的冠状动脉小动脉会对该药物表现出持续性扩张，因为在这些条件下内在逃逸机制将不存在。为了验证这些假设，我们在连续给予硝酸甘油（冠状动脉内输注或心外膜灌注）期间，使用活体荧光显微镜（n = 17只狗）在两个时间点测量犬冠状动脉微血管的直径变化：早期（1 - 3分钟），此时冠状动脉血流速度增加；晚期（15 - 20分钟），血流速度恢复至对照水平后。为了研究在没有自动调节影响的情况下冠状动脉小动脉的反应，我们测量了分离的犬冠状动脉小动脉对不同剂量硝酸甘油的直径变化（n = 8条血管，最大直径81±4微米）。在硝酸甘油输注的早期阶段（1、3和10微克·千克⁻¹·分钟⁻¹），冠状动脉小动脉分别扩张了4±1%、7±2%和13±2%（均P < 0.05），而小动脉分别扩张了1±2%、3±1%和4±1%（较高剂量时P < 0.05）。测量的冠状动脉血流速度增加了45±15%（3微克·千克⁻¹·分钟⁻¹，P < 0.05）。在1至3分钟之间，灌注硝酸甘油（10⁻⁵ M）使冠状动脉小动脉扩张了17±5%（P < 0.05），但未使小动脉扩张。在冠状动脉内输注硝酸甘油（3微克·千克⁻¹·分钟⁻¹）15 - 20分钟后，冠状动脉小动脉的直径和冠状动脉血流速度恢复至对照水平，而小动脉的扩张仍显著，为4±1%。通过心外膜灌注硝酸甘油引起的冠状动脉小动脉扩张在第15 - 20分钟时也减弱至对照值，而观察到小动脉有5±2%的扩张（P < 0.05）。在体外，硝酸甘油引起冠状动脉小动脉剂量依赖性扩张至其最大直径，并持续20分钟。因此，硝酸甘油可扩张冠状动脉小动脉和小动脉。在体内，小动脉的扩张是短暂的，而动脉的扩张是持续的。在体外，扩张是持续的。由于体外微血管能够持续扩张20分钟，我们得出结论，体内小动脉扩张的减弱与对硝酸甘油扩张的自动调节逃逸有关。
