Stereoselective Differences In The Vasorelaxing Effects Of S(+) And R(-) Ketamine On Rat Isolated Aorta

Background: S(+) ketamine, because of its higher anesthetic potency and lower risk of psychotomimetic reactions, has been suggested to be superior to presently available racemic ketamine, The racemate is a direct vasodilator in vivo, and thus the authors investigated the vasorelaxing effects of ketamine enantiomers on rat aorta.Methods: Rat isolated aortic rings with and without endothelium were contracted with 3.10(-7) M norepinephrine, Then 10(-5) to 3.10(-3) M S(+), R(-), or racemic ketamine were added cumulatively, Vascular responses to ketamine were further studied in rings pretreated with the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K- channel antagonist glibenclamlde, and the L-type calcium channel blocking agent D888.Results: Ketamine enantiomers and the racemate produced concentration-dependent vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker compared with R(-) ketamine and the racemate reflected by the half-maximum effective concentration (EC50) values of 11.6.10(-4) 4.8.10(-4), and 6.10(-4) M, respectively, Removal of the endothelium and NNLA or glibenclamide pretreatment did not significantly alter the vasorelaxing effect of ketamine, In contrast, D888 pretreatment significantly shifted the concentration-effect curves of both S(+) and R(-) ketamine rightward (EC50) values of 18.9.10(-4) and 8.5.10(-4) M, respectively, whereas the difference between the isomers was not affected.Conclusions: Vasorelaxation by ketamine enantiomers is quantitatively stereoselective: The effect of S(+) ketamine is significantly weaker compared with that of the racemate and R(-) ketamine, This stereoselective difference is not due to nitric oxide release, activation of adenosine triphosphate-sensitive potassium channels, or differential inhibition of L-type calcium channels.