Volatile anesthetic actions on contractile proteins in membrane- permeabilized small mesenteric arteries

T. Akata, W. A. Boyle

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background: Volatile anesthetics have been shown to have vasodilating or vasoconstricting actions tn vitro that may contribute to their cardiovascular effects in vivo. However, the precise mechanisms of these actions in vitro have not been fully elucidated. Moreover, there are no data regarding the mechanisms of volatile anesthetic action on small resistance arteries, which play a critical role in the regulation of blood pressure and blood flow. Methods: With the use of isometric tension recording methods, volatile anesthetic actions were studied in intact and β-escin-membrane-permeabilized smooth muscle strips from rat small mesenteric arteries. In experiments with intact muscle, the effects of halothane (0.25-5.0%), isoflurane (0.25-5.0%), and enflurane (0.25-5.0%) were investigated on high K+-induced contractions at 22°C and 35°C. All experiments were performed on endothelium-denuded strips in the presence of 3 μM guanethidine and 0.3 μM tetrodotoxin to minimize the influence of nerve terminal activities. In experiments with membrane-permeabilized muscle, the effects of halothane (0.5-4.0%), isoflurane (0.5-4.0%), and enflurane (0.5-4.0%) on the half-maximal and maximal Ca2+-activated contractions were examined at 22°C in the presence of 0.3 μM ionomycin to eliminate intracellular Ca2+ stores. Results: in the high K+-stimulated intact muscle, all three anesthetics generated transient contractions, which were followed by sustained vasorelaxation. The IC50 values for this vasorelaxing action of halothane, isoflurane, and enflurane were 0.47 vol% (0.27 mM), 0.66 vol% (0.32 mM), and 0.53 vol% (0.27 mM), respectively, at 22 °C and were 3.36 vol% (0.99 mM), 3.07 vol% (0.69 mM), and 3.19 vol% (0.95 mM), respectively, at 35°C. Ryanodine (10 μM) eliminated the anesthetic-induced contractions but had no significant effect on the anesthetic-induced vasorelaxation in the presence of high K+. In addition, no significant differences were observed in the dose dependence of the direct vasodilating action among these anesthetics with or without ryanodine at either the low or the high temperature. However, significant differences were observed in the vasoconstricting actions among the anesthetics, and the order of potency was halothane > enflurane > isoflurane. The Ca2+-tension relation in the membrane-permeabilized muscle yielded a half-maximal effective Ca2+ concentration (EC50) of 2.02 μM. Halothane modestly but significantly inhibited 3 μM (approximately the EC50) and 30 μM (maximal) Ca2+-induced contractions. Enflurane slightly but significantly inhibited 3 μM but not 30 μM Ca2+ contractions. Isoflurane did not significantly inhibit either 3 μM or 30 μM Ca2+ contractions. Conclusions: Halothane, isoflurane, and enflurane have both vasoconstricting and vasodilating actions on isolated small splanchnic resistance arteries. The direct vasoconstricting action appears to result from Ca2+ release from the ryanodine-sensitive intracellular Ca2+ store. The vasodilating action of isoflurane in the presence of high K+ appears to be attributable mainly to a decrease in intracellular Ca2+ concentration, possibly resulting from inhibition of voltage-gated Ca2+ channels. In contrast, the vasodilating actions of halothane and enflurane in the presence of high K+ appears to involve inhibition of Ca2+ activation of contractile proteins as well as a decrease in intracellular Ca2+ concentration in smooth muscle.

Original languageEnglish
Pages (from-to)700-712
Number of pages13
JournalAnesthesiology
Volume82
Issue number3
DOIs
StatePublished - Jan 1 1995

Keywords

  • Anesthetics, volatile: enflurane; halothane; isoflurane
  • Artery: resistance
  • Membrane, permeabilization: β-escin
  • Muscle, smooth: vascular

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