Effect of Ketamine on Phenylephrine-Induced Contraction in Isolated Rat Thoracic Aorta

Abstract

Background: Ketamine causes a dose-dependent vasodilation of a norepinephrine-precontracted pulmonary arterial ring. The goals of the present in vitro study were to investigate the effects of ketamine on phenylephrine-induced contraction and to elucidate its cellular mechanism. Methods: Following endothelial denudation, isolated thoracic aortic rings were suspended for isometric tension recording. Contractile response to 60 mM KCl (potassium chloride) was measured in the absence or presence of ketamine ( , , M) in the rings. Phenylephrine dose ( to M)-response curves were generated in the absence or presence of ketamine. In rings pretreated with verapamil ( M) or with combined verapamil ( M) and ryanodine ( M), phenylephrine dose-response curves were also generated in the absence or presence of ketamine. Results: Ketamine attenuated the contractile response to 60 mM KCl compared with rings without ketamine in a concentration-dependent manner, and ketamine ( , , M) caused a rightward shift of the dose-response curve to phenylephrine in a concentration-dependent manner. In verapamil M pretreated rings, ketamine M attenuated phenylephrine-induced contraction compared to rings without ketamine, but a low-dose of ketamine ( , M) had no effect. In rings pretreated with combined verapamil M and ryanodine M, ketamine M attenuated phenylephrine-induced contraction compared with rings without ketamine. Conclusions: These results indicate that clinically relevant concentration ( M) of ketamine attenuates phenylephrine-induced contraction by inhibiting the L-type calcium channel.