Isoflurane attenuates cAMP-mediated vasodilation in rat microvessels.

Abstract

Endothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation. Fifty-three subepicardial coronary arteries (diameter, 103 +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L, concentration response curves to the nonselective beta-adrenergic agonist isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence of absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls. Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.