Inhibitory effects of etomidate and ketamine on adenosine triphosphate-sensitive potassium channel relaxation in canine pulmonary artery.
BACKGROUND
The authors recently demonstrated that etomidate and ketamine attenuated endothelium-dependent pulmonary vasorelaxation mediated by nitric oxide and Ca -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 x 10(-6) and 5 x 10(-5) m) and ketamine (5 x 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 x 10(-6) m) only inhibited the vasorelaxant response to lemakalim in endothelium intact rings, whereas a higher concentration of etomidate (5 x 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 x 10(-5) and 10(-5) 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 an inhibitory effect on the cyclooxygenase pathway. Both anesthetics inhibit K + ATP -mediated pulmonary vasorelaxation a direct effect on pulmonary vascular smooth muscle.
Sohn
Ju-Tae
JT
Center for Anesthesiology Research, Division of naesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Murray
Paul A
PA
D018528:ATP-Binding Cassette Transporters; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology; D005045:Etomidate / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D054086:KATP Channels; D007649:Ketamine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D016861:Cyclooxygenase Inhibitors; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D007649:Ketamine; D010208:Papaverine; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin; D005045:Etomidate