VOLATILE ANESTHETICS AND AGONIST-INDUCED CONTRACTIONS IN PORCINE CORONARY-ARTERY SMOOTH-MUSCLE AND CA2-MUSCLE CELLS( MOBILIZATION IN CULTURED IMMORTALIZED VASCULAR SMOOTH)

Background: These experiments addressed four specific questions. Do is oflurane and halothane (0.5-3.0% in the gas phase) inhibit contraction s evoked in isolated porcine coronary artery rings (without endotheliu m) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, a nd F-? Are contractions evoked by phorbol-activated protein kinase C i nhibited by the anesthetics? In a well-characterized vascular smooth m uscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin-induced Ca2+ mobilization? Do the anesthetic s inhibit intracellular Ca2+ mobilization via facilitated cAMP formati on? 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 contr actions evoked by serotonin and F- but not those induced by endothelin -1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3X10(-5) M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ respo nses evoked by endothelin 10(-8) M were more resistant to anesthetic i nhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol-induced re sponses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. N either anesthetic facilitated cAMP formation. Conclusions: Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizi ng 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-b ut the mechanism does not depend upon increased cAMP.