Propofol attenuates the contractile response induced by release of cellularly sequestered calcium isolated from human omental arteries and veins

Abstract

A side effect of the intravenous propofol is hypotension. The underlying mechanism has been suggested to be a decrease in sympathetic activity and/or a direct effect on vascular smooth muscle. In the present study, the direct effect of propofol on human vascular smooth muscle was investigated, especially concerning the modulation of propofol on muscle contraction involving extra- or intracellular calcium. Isolated human omental arteries and veins were obtained from patients undergoing abdominal surgery and mounted in organ baths containing aerated modified Krebs-Ringer buffer solution. Changes in circular isometric smooth muscle tension in response to the administration of propofol were measured. Contractile responses induced by the stable thromboxane A2 analogue U46619, caffeine and KCI in the presence or absence of propofol were also measured. U46619 elicits its contractile response via IP3-mediated release of cellularly sequestered calcium and caffeine elicits its contractile response predominantly via ryanodine receptor-mediated release of cellularly sequestered calcium. On the other hand, KCI elicits via influx of extracellular calcium through voltage-dependent calcium channels. A Ca2+-free buffer solution was used for the experiments with U46619 and caffeine, whereas a normal buffer solution was used for the experiments with KCI. Propofol (10−3 M) induced a contraction in both arteries and veins. Conversely, propofol concentration-dependently attenuated the contraction elicited by U46619 and caffeine in the absence of extracellular calcium and the contraction elicited by KCI in the presence of extracellular calcium. The threshold concentration for the effect of propofol was lower for the U46619-induced contraction (10−5 M) and the caffeine-induced contraction (10−5 M and 10−4.5 for artery and vein respectively) than for the KCI-induced contraction (10−4 M). The present results suggest that propofol, at concentrations likely to occur clinically, attenuates contraction involving release of cellularly sequestered calcium. At higher concentrations of propofol, a contraction-attenuating effect of a different nature appears, which seems not solely to involve effects on intracellular calcium fluxes.