The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 2)

Background The precise mechanisms behind the direct inhibitory action of sevoflurane on vascular smooth muscle have not been fully elucidated. Methods Endothelium-denuded smooth muscle strips were prepared from rat small mesenteric arteries. Isometric force and intracellular Ca2+ concentration ([Ca2+]i) were measured simultaneously in the fura-2-loaded strips. In another series of experiments, only isometric force was measured in the beta-escin-membrane-permeabilized strips. Results Sevoflurane (3-5%) inhibited the increases in both the [Ca2+]i and the force induced by either norepinephrine (0.5-10 microm) or 40 mm K+. Sevoflurane still inhibited the increase in [Ca2+]i induced by norepinephrine after depletion of intracellular Ca2+ stores with ionomycin, although it little influenced the increase in [Ca2+]i induced by norepinephrine after treatment with verapamil. In the fura-2-loaded membrane-intact muscle, sevoflurane caused a rightward shift of Ca2+-force relation during force development to stepwise increment of extracellular Ca2+ concentration during 40-mm K+ depolarization in either the presence or the absence of norepinephrine. In contrast, sevoflurane did not influence Ca2+-activated contraction in the beta-escin-permeabilized muscle, in which alpha-adrenergic receptor coupling was not retained. Conclusions The inhibitory effects of sevoflurane on both norepinephrine- and potassium chloride (KCl)-induced contractions are caused by reduction of [Ca2+]i in vascular smooth muscle and inhibition of the myofilament Ca2+ sensitivity. The [Ca2+]i-reducing effect of sevoflurane observed in both the norepinephrine- and the K+-stimulated muscle is mainly caused by inhibition of voltage-gated Ca2+ influx. The inhibitory effect of sevoflurane on Ca2+ activation of contractile proteins seems to be mediated by the cell membrane or by some diffusible substances that are lost in the beta-escin-permeabilized cells.