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

Ok, Seong Ho; Sohn, Ju Tae; Lee, Ju Hye; Park, Mi Young; Shin, Il Woo; Lee, Heon Keun; Chung, Young Kyun

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 (5x10(-5), 10(-4), 10(-3) M) in the rings. Phenylephrine dose (10(-8) to 10(-5) M)-response curves were generated in the absence or presence of ketamine. In rings pretreated with verapamil (10(-5) M) or with combined verapamil (10(-5) M) and ryanodine (2x10(-5) 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 (5x10(-5), 10(-4), 10(-3)M) caused a rightward shift of the dose-response curve to phenylephrine in a concentration-dependent manner. In verapamil 10(-5) M pretreated rings, ketamine 10(-3) M attenuated phenylephrine-induced contraction compared to rings without ketamine, but a low-dose of ketamine (5x10(-5), 10(-4)M) had no effect. In rings pretreated with combined verapamil 10(-5) M and ryanodine 2 x 10(-5) M, ketamine 10(-3) M attenuated phenylephrine-induced contraction compared with rings without ketamine.
CONCLUSIONS
These results indicate that clinically relevant concentration (5 x 10(-5) M) of ketamine attenuates phenylephrine-induced contraction by inhibiting the L-type calcium channel.