15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and 12-deoxyphorbol-13-isobutyrate-20-acetate

Protein kinase C (PKC), important in signal transduction, may help generate and maintain vascular smooth muscle tone. We sought to examine the effect of the volatile anesthetics isoflurane and halothane on PKC agonist-induced vasoconstriction and PKC inhibitor-induced vasorelaxation. Subepicardial resistance arteries were dissected from rat hearts. Changes in vessel diameters were monitored in response to the membrane-bound PKC agonist 12-deoxyphorbol-13-isobutyric-20-acetate (PBE) 10(-8)-10(-7) M or the cytosolic PKC agonist oleic acid 10(-7)-10(-5.5) M either in the presence of isoflurane 1.15%, isoflurane 2.3%, halothane 0.77%, halothane 1.54%, or no volatile anesthetics (control). In addition, after preconstriction with the thromboxane analog U46619 1 microM, relaxation responses to the PKC inhibitor staurosporine 10(-8)-10(-7) M were examined in the presence or absence of the anesthetics as above. PBE-induced constriction was attenuated by either concentration of halothane (P < 0.05) but was unaltered by isoflurane (P > 0.5). Oleic acid-induced constriction was abolished by halothane (P < 0.001) but enhanced by isoflurane (P < 0.01). Staurosporine-induced relaxation of U46619-preconstricted vessels was attenuated by isoflurane (P < 0.05) but unaltered by halothane (P > 0.3). We conclude that isoflurane may enhance cytosolic PKC-mediated vasoconstriction, whereas halothane may attenuate both cytosolic and membrane-bound PKC-mediated vasoconstriction.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alkaloids; Anesthetics, Inhalation; Animals; Coronary Vessels; Drug Interactions; Drug Synergism; Enzyme Inhibitors; Female; Halothane; Isoflurane; Male; Oleic Acid; Oleic Acids; Phorbol Esters; Prostaglandin Endoperoxides, Synthetic; Protein Kinase C; Rats; Rats, Wistar; Staurosporine; Thromboxane A2; Vasoconstrictor Agents; Vasodilator Agents