Inhibitory effects of etomidate and ketamine on adenosine triphosphate-sensitive potassium channel relaxation in canine pulmonary artery

Abstract

Background: The authors recently demonstrated that etomidate and ketamine attenuated endothelium-dependent pulmonary vasorelaxation mediated by nitric oxide and Ca2+-activated K+ channels. In the current study, they tested the hypothesis that these intravenous anesthetics inhibit pulmonary vasorelaxation mediated by adenosine triphosphate-sensitive potassium (K+ATP) channel activation. Methods: Endothelium intact and denuded pulmonary arterial rings were suspended in organ chambers for isometric tension recording. The effects of etomidate (5 × 10-6 and 5 × 10-5 M) and ketamine (5 × 10-5 and 10-4 M) on vasorelaxation responses to lemakalim (K+ATP channel activator), prostacyclin, and papaverine were assessed in phenylephrine-precontracted rings. The effect of cyclooxygenase inhibition with indomethacin was assessed in some protocols. Results: Etomidate (5 × 10-6 M) only inhibited the vasorelaxant response to lemakalim in endothelium intact rings, whereas a higher concentration of etomidate (5 × 10-5 M) inhibited relaxation in both intact and endothelium-denuded rings. Pretreatment with indomethacin abolished the endothelium-dependent attenuation of lemakalim-induced relaxation caused by etomidate. Ketamine (5 × 10-5 and 10-4 M) inhibited the relaxation response to lemakalim to the same extent in both endothelium-intact and -denuded rings, and this effect was not prevented by indomethacin pretreatment. Etomidate and ketamine had no effect on the relaxation responses to prostacyclin or papaverine. Conclusions: These results indicate that etomidate, but not ketamine, attenuates the endothelium-dependent component of lemakalim-induced pulmonary vasorelaxation via an inhibitory effect on the cyclooxygenase pathway. Both anesthetics inhibit K+ATP-mediated pulmonary vasorelaxation via a direct effect on pulmonary vascular smooth muscle.