Ketamine stereoselectively affects vasorelaxation mediated by ATP-sensitive K+ channels in the rat aorta

Abstract

Background: The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K+ channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K+ channel opener in the isolated rat aorta. Methods: Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10-7 M), vasorelaxation in response to an ATP-sensitive K+ channel opener levcromakalim (10-8 to 10-5 M) or a nitric oxide donor sodium nitroprusside (10-1 to 10-5 M) was obtained. Glibenclamide (10-5 M), S(+) ketamine (10-4 M), or ketamine racemate (10-5 to 10-4 M) was applied 15 min before addition of phenylephrine. Results: Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K+ channel antagonist glibenclamide (10-5 M) in the aorta with or without endothelium. Ketamine racemate (3 x 10-5 to 10-4 M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium. Conclusion: In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K+ channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation via ATP-sensitive K+ channels in the conduit artery.