Effect of propofol on norepinephrine-induced increases in [Ca2+](i) and force in smooth muscle of the rabbit mesenteric resistance artery

Abstract

Background: Propofol (2,6-diisopropylphenol) possesses vasodilating activity in vivo and in vitro. The propofol-induced relaxation of agonist- induced contractions in small resistance arteries has not been clarified. Methods: The effect of propofol was examined on the contractions induced by norepinephrine and high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The effects of propofol on the [Ca2+](i) mobilization induced by norepinephrine and high K+ were studied by simultaneous measurement of [Ca2+](i) using Fura 2 and isometric force in ryanodine-treated strips. Results: Propofol attenuated the contractions induced by high K+ and norepinephrine, the effect being greater on the high K+-induced contraction than on the norepinephrine-induced contraction. In Ca2+-free solution, norepinephrine produced a transient contraction resulting from the release of Ca2+ from storage sites that propofol attenuated. In ryanodine-treated strips, propofol increased the resting [Ca2+](i) but attenuated the increases in [Ca2+](i) and force induced by both high K+ and norepinephrine. In the presence of nicardipine, propofol had no inhibitory action on the residual norepinephrine-induced [Ca2+)(i) increase, whereas it still modestly increased resting [Ca2+](i), as in the absence of nicardipine. Conclusions: In smooth muscle of the rabbit roesenteric resistance artery, propofol attenuates norepinephrine-induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx through L-type Ca2+ channels. Propofol also increased resting [Ca2+](i), possibly as a result of an inhibition of [Ca2+](i) removal mechanisms. These results may explain in part the variety of actions seen with propofol in various types of vascular smooth muscle.