In vivo and in vitro vasoactive reactions of coronary arteriolar microvessels to nitroglycerin

Abstract

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.