Volatile anesthetics and agonist-induced contractions in porcine coronary artery smooth muscle and Ca2+ mobilization in cultured immortalized vascular smooth muscle cells

M. Ozhan, J. C. Sill, P. Atagunduz, R. Martin, Z. S. Katusic

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: These experiments addressed four specific questions. Do isoflurane and halothane (0.5-3.0% in the gas phase) inhibit contractions evoked in isolated porcine coronary artery rings (without endothelium) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, and F-? Are contractions evoked by phorbol-activated protein kinase C inhibited by the anesthetics? In a well-characterized vascular smooth muscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin- induced Ca2+ mobilization? Do the anesthetics inhibit intracellular Ca2+ mobilization via facilitated cAMP formation? Methods: Tension was measured in rings suspended in organ chambers. Apparent intracellular Ca2+ was estimated in cells using indo-1 and flow cytometry. Cyclic AMP was measured by radioimmunoassay. Results: At the anesthetic concentrations examined, isoflurane attenuated contractions evoked by serotonin and F- but not those induced by endothelin-1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3 x 10-5 M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ responses evoked by endothelin 10-8 M were more resistant to anesthetic inhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol- induced responses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. Neither anesthetic facilitated cAMP formation. Conclusions: Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizing agonists-by a cellular action beyond the receptor level-but did not inhibit phorbol activated protein kinase C. Serotonin- and endothelin-induced Ca2+ mobilization was inhibited by isoflurane and halothane-but the mechanism does not depend upon increased cAMP.

Original languageEnglish (US)
Pages (from-to)1102-1113
Number of pages12
JournalAnesthesiology
Volume80
Issue number5
DOIs
StatePublished - 1994

Keywords

  • Anesthetics, volatile: halothane; isoflurane
  • Arteries, coronary: pig
  • Cell culture, smooth muscle: A10; A7r5
  • Ions: calcium; fluoride
  • Nucleotides: cyclic adenosine monophosphate
  • Pharmacology: endothelin; fluoride; phorbol dibutyrate; serotonin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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