Ketamine enantiomers differentially relax isolated coronary artery rings

Abstract

Background and objective: It has been shown that racemic ketamine increases coronary blood flow and that this effect is at least in part due to a direct vasorelaxing effect of this substance. This study was designed to determine whether ketamine might stereoselectively relax isolated porcine coronary arteries. Methods: Using the model of isolated vessels we studied the effects of S(+) ketamine, R(−) ketamine, and racemic ketamine (5-500 μg mL−1) on artery strips pre-contracted by either potassium chloride (KCl) or prostaglandin F2α (PGF2α). To elucidate possible mechanisms of action these experiments were repeated in the presence of one of the following compounds: Nω-nitro-L-arginine (L-NNA), indomethacin, glibenclamide, and tetraethylammonium (TEA) chloride, an inhibitor of the BKCa K+ channel. Results: Both isoforms and racemic ketamine relaxed isolated coronary arteries in a concentration-dependent manner in concentrations beyond those used in clinical practice. S(+) ketamine exerted the strongest vasorelaxing effect, followed by racemic ketamine and R(−) ketamine. Pretreatment with L-NNA, indomethacin, or glibenclamide did not alter the vasodilating properties of ketamine, whereas TEA chloride significantly attenuated the vasorelaxing effects of all the three forms of ketamine. Conclusions: Ketamine dilates coronary arteries in vitro when administered in high concentrations. There is a stereoselective difference with a stronger vasorelaxing effect of S(+) ketamine compared to racemic and R(−) ketamine. The impact of TEA chloride suggests that the activation of the BKCa channel may contribute to the vasodilating effect of ketamine.