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

Abstract

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? 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. 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. 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.