ISOFLURANE ATTENUATES CAMP-MEDIATED VASODILATION IN RAT MICROVESSELS

Background Endothelium-dependent vasodilation mediated by cGMP is know n to be attenuated by the inhalational anesthetic isoflurane. The pres ent study examines the effect of isoflurane on beta-adrenergic and cAM P-mediated vasodilation.Methods and Results Fifty-three subepicardial coronary arteries (diameter, 103+/-13 mu m) from Wistar rats were stud ied in vitro in a pressurized (40 mm Hg), no-flow state with use of op tical density video detection system. After preconstriction of vessels with the thromboxane A? analogue U46619 10(-6) mol/L, concentration r esponse curves to the nonselective beta-adrenergic agonist isoproteren ol, the G(s) protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodieste rase inhibitor R020-1724 were obtained either in the presence or absen ce (control) of 2% isoflurane. Relaxations to all the agents tested we re significantly reduced in the presence of isoflurane compared with c ontrols. Conclusions Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not d ue to enhancement of cAMP phosphodiesterase.