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 pot assium channels, but the role of the arterioles (resistance vessels) i n these responses is controversial. Methods: Medium porcine coronary a rterioles (internal diameter, 172 +/- 51 [SD] mu m) were placed In a c hamber supplied with Kreb's buffer, pressurized (40 mmHg), and precons tructed with acetylcholine (10(-8)-10(-6) M). Vascular diameter (VD) w as assessed using an optical density video-detection system. Isofluran e (in 95% oxygen and 5% carbon dioxide) was added to buffer using a me mbrane oxygenator supplied by a calibrated vaporizer. In series 1 (n = 14), 2% isoflurane was administered according to an abrupt (ISO-A) an d 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 p otassium channel antagonist) or 8-phenyltheophylline (a nonselective a denosine receptor antagonist), respectively. In series 4 (n = 5), vali dation 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 es sentially concentration-dependent increases in VD. At 2% Isoflurane, t he increases in VD were greater during ISO-A than ISO-G.. Glibenclamid e, but not 8-phenyltheophylline, attenuated isoflurane-induced increas es in VD. Both sodium nitroprusside and adenosine diphosphate caused d ose-dependent increases in VD. Isoflurane caused equivalent concentrat ion-dependent increases in VD during acetylcholine and U46619. Conclus ions: Isoflurane is a concentration-dependent dilator of porcine coron ary arterioles preconstricted with acetylcholine or U46619. This effec t is blunted by gradual administration, suggesting that the vessels ma y adapt to the relaxing effects of isoflurane. Isoflurane-induced dila tion of coronary arterioles is mediated by the ATP-sensitive potassium channels but not by the adenosine receptors.