Isoflurane-induced Dilation of Porcine Coronary Arterioles Is Mediated by ATP-sensitive Potassium Channels 

Background Isoflurane causes increases in coronary blood flow in vivo, which are mediated by the adenosine triphosphate (ATP)-sensitive potassium channels, but the role of the arterioles (resistance vessels) in these responses is controversial. Methods Medium porcine coronary arterioles (internal diameter, 172 +/- 51 [SD] microm) were placed in a chamber supplied with Kreb's buffer, pressurized (40 mmHg), and preconstricted with acetylcholine (10(-8)-10(-6) M). Vascular diameter (VD) was assessed using an optical density video-detection system. Isoflurane (in 95% oxygen and 5% carbon dioxide) was added to buffer using a membrane oxygenator supplied by a calibrated vaporizer. In series 1 (n = 14), 2% isoflurane was administered according to an abrupt (ISO-A) and gradual (ISO-G) protocol. In series 2 (n = 13) and 3 (n = 6), ISO-A (1.5%) was assessed before and after glibenclamide (an ATP-sensitive potassium channel antagonist) or 8-phenyltheophylline (a nonselective adenosine receptor antagonist), respectively. In series 4 (n = 5), validation studies were performed using sodium nitroprusside and adenosine diphosphate to verify that the vascular smooth muscle and endothelium of the vessels were functionally intact. In series 5 (n = 6), ISO-A (0.75 and 1.5%) was compared during preconstriction with acetylcholine and the thromboxane analog U46619 (10(-6) M). Results ISO-G caused essentially concentration-dependent increases in VD. At 2% isoflurane, the increases in VD were greater during ISO-A than ISO-G. Glibenclamide, but not 8-phenyltheophylline, attenuated isoflurane-induced increases in VD. Both sodium nitroprusside and adenosine diphosphate caused dose-dependent increases in VD. Isoflurane caused equivalent concentration-dependent increases in VD during acetylcholine and U46619. Conclusions Isoflurane is a concentration-dependent dilator of porcine coronary arterioles preconstricted with acetylcholine or U46619. This effect is blunted by gradual administration, suggesting that the vessels may adapt to the relaxing effects of isoflurane. Isoflurane-induced dilation of coronary arterioles is mediated by the ATP-sensitive potassium channels but not by the adenosine receptors.