Partially endothelium-dependent relaxing effect of ketamine on the canine basilar artery in vitro.
The influence of the endothelium on the vasodilator effect of ketamine and its possible mechanism of action on intracellular calcium levels were investigated. We conducted experiments in vitro on canine basilar arteries precontracted with 5-HT and with potassium at high concentrations. Ketamine (10(-6) to 10(-3) M), added cumulatively, relaxed both 5-HT and high-K(+)-induced contraction of basilar arteries (with or without endothelium) in a dose-dependent manner. The ED50s of ketamine for relaxation of 5-HT and high-K(+)-induced contraction for intact endothelium were 3 x 10(-4) M and 6 x 10(-4) M, respectively, and for denuded preparations, 7 x 10(-4) M and 15 x 10(-4) M, respectively. Methylene blue, which blocks the release and/or the effect of endothelium derived relaxing factor, significantly attenuated the relaxation effect of ketamine on the basilar artery. Our results indicate that the endothelium may be responsible for a part of the vasodilator effect of ketamine. We also examined the effect of pretreatment of basilar artery with ketamine (5 x 10(-4) M) on intracellular calcium levels when contraction was induced by 5-HT or by high K+ concentrations. Ketamine significantly inhibited the phase of the contraction induced by high K+. Thus, the vasodilator effect of ketamine may be mediated by inhibition of calcium influx and by the release of EDRF.
Chung
H C
HC
Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Ho
S T
ST
Ho
W
W
Yen
M H
MH
Lin
C Y
CY
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D007649:Ketamine; D002118:Calcium