Protein kinase C-induced contraction is inhibited by halothane but enhanced by isoflurane in rat coronary arteries.
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.
Park
K W
KW
Department of Anesthesia, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Dai
H B
HB
Lowenstein
E
E
Sellke
F W
FW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000470:Alkaloids / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004347:Drug Interactions; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000470:Alkaloids; D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D009829:Oleic Acids; D010703:Phorbol Esters; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D019301:Oleic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007530:Isoflurane; D011493:Protein Kinase C; D019311:Staurosporine; D006221:Halothane