IN-VIVO AND IN-VITRO VASOACTIVE REACTIONS OF CORONARY ARTERIOLAR MICROVESSELS TO NITROGLYCERIN

The actions of nitroglycerin on the coronary microcirculation are cont roversial, with some laboratories reporting that coronary arterioles d ilate to the drug and others report ing that they do not. Our goal was to reconcile these disparate observations. Specifically, we hypothesi zed that dilation of coronary arterioles by nitroglycerin is overwhelm ed by intrinsic autoregulatory escape mechanisms. Accordingly, we proj ected 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 dru g, because intrinsic escape mechanisms would be absent under these con ditions. To test these hypotheses, we measured diameter changes of can ine coronary microvessels in vivo during continuous nitroglycerin admi nistration (intracoronary infusion or epicardial suffusion) using intr avital 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. To s tudy responses of coronary arterioles in the absence of autoregulatory influences, we measured the diameter of isolated canine coronary arte rioles to varying doses of nitroglycerin (n = 8 vessels, maximal diame ter 81 +/- 4 mu m). During the early phase of nitroglycerin infusion ( 1, 3, and 10 mu g . 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 mu g . kg(-1) . min(-1), P < 0.05). Suffusion of nitr oglycerin (10(-5) M) dilated coronary arterioles, but not small arteri es, by 17 +/- 5% (P < 0.05) between 1 and 3 min. After 15-20 min of ni troglycerin (3 mu g . kg(-1) . min(-1) by intracoronary infusion), dia meters of coronary arterioles and coronary artery blood velocity retur ned to control, whereas dilation of small arteries remained significan t at 4 +/- 1%. Coronary arteriolar dilation by epicardial suffusion of nitroglycerin also waned to control values by 15-20 min, whereas dila tion of small arteries was observed: 5 +/- 2% (P < 0.05). In vitro, ni troglycerin caused dose-dependent dilation of coronary arterioles to t heir maximal diameter, which was sustained for 20 min. Thus nitroglyce rin dilates coronary arterioles and small arteries. The dilation in vi vo is transient for arterioles but sustained for arteries. In vitro, t he dilation is sustained. Because microvessels in vitro are capable of sustaining dilation for 20 min, we conclude that the waning of arteri olar dilation in vivo is related to autoregulatory escape from dilatio n by nitroglycerin.