Halothane and enflurane attenuate pulmonary vasodilation mediated by adenosine triphosphate-sensitive potassium channels compared to the conscious state

Background: Adenosine triphosphate (ATP)-sensitive potassium (K-ATP(+)) channels play an important role in pulmonary vasoregulation However, the effects of volatile anesthetics on K-ATP(+) channel-mediated pulmonary vasoregulation have not been eluddated The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective K-ATP(+) channel agonist lemakalim (BRL38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to K-ATP(+) channel activation. Method: Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood now during gradual (similar to 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11(alpha),9(alpha)-epoxymethanoprostaglandin F-2 alpha), the pulmonary vascular dose-response relationship for the K-ATP(+) agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha(1) adrenoreceptors, arginine vasopressin V-1-receptors, and angiotensin II receptors. The effect of the K-ATP(+) antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs. Results: Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block. Conclusion: These results indicate that halothane and enflurane act to reduce the magnitude of K-ATP(+) channel-mediated pulmonary vasodilation. Reflex pulmonary vasoconstriction resulting from K-ATP(+)-mediated systematic hypotension does not alter the magnitude of the pulmonary vasodilator response to lemakalim nor is it responsible for the attenuated response to K-ATP(+), channel activation during halothane anesthesia.