The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries (part 2): mechanisms of endothelium-independent vasorelaxation.
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.
Akata
T
T
Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. akata@kuaccm.med.kyushu-u.ac.jp
Izumi
K
K
Nakashima
M
M
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004928:Escin / Q000494:pharmacology; D005456:Fluorescent Dyes; D005470:Fluorometry; D016257:Fura-2; D008297:Male; D008638:Mesenteric Arteries; D008738:Methyl Ethers / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D018685:Anesthetics, Inhalation; D005456:Fluorescent Dyes; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D000077149:Sevoflurane; D011189:Potassium Chloride; D004928:Escin; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine