The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries (part 2) : Mechanisms of endothelium-independent vasorelaxation

• Published in: Anesthesiology (Philadelphia) 2000-05, Vol.92 (5), p.1441-1453
• Main Authors: AKATA, T, IZUMI, K, NAKASHIMA, M
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Anesthetics, Inhalation - pharmacology; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Calcium - metabolism; Drug Interactions; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Escin - pharmacology; Fluorescent Dyes; Fluorometry; Fura-2; Male; Medical sciences; Mesenteric Arteries; Methyl Ethers - pharmacology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Neuropharmacology; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley; Sevoflurane; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200005000-00035

The precise mechanisms behind the direct inhibitory action of sevoflurane on vascular smooth muscle have not been fully elucidated. 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. 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. 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.