Isoflurane Attenuates cAMP-Mediated Vasodilation in Rat Microvessels

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Abstract
Background 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 β-adrenergic and cAMP-mediated vasodilation. Methods and Results Fifty-three subepicardial coronary arteries (diameter, 103±13 μm) 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 A 2 analogue U46619 10 −6 mol/L, concentration response curves to the nonselective β-adrenergic agonist isoproterenol, the G S 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 or absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls. Conclusions Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.