Park K W, Dai H B, Lowenstein E, Sellke F W
Department of Anesthesia, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Anesth Analg. 1996 Aug;83(2):286-90. doi: 10.1097/00000539-199608000-00015.
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.
蛋白激酶C（PKC）在信号转导中起重要作用，可能有助于产生并维持血管平滑肌张力。我们试图研究挥发性麻醉药异氟烷和氟烷对PKC激动剂诱导的血管收缩以及PKC抑制剂诱导的血管舒张的影响。从大鼠心脏中分离出心外膜阻力动脉。在存在1.15%异氟烷、2.3%异氟烷、0.77%氟烷、1.54%氟烷或无挥发性麻醉药（对照）的情况下，监测血管直径对膜结合型PKC激动剂12 - 脱氧佛波醇 - 13 - 异丁酸 - 20 - 乙酸酯（PBE）10(-8)-10(-7) M或胞质型PKC激动剂油酸10(-7)-10(-5.5) M的反应变化。此外，在用血栓素类似物U46619 1 microM预收缩后，在上述麻醉药存在或不存在的情况下，检测对PKC抑制剂星形孢菌素10(-8)-10(-7) M的舒张反应。PBE诱导的收缩被两种浓度的氟烷减弱（P < 0.05），但未被异氟烷改变（P > 0.5）。油酸诱导的收缩被氟烷消除（P < 0.001），但被异氟烷增强（P < 0.01）。星形孢菌素诱导的U46619预收缩血管的舒张被异氟烷减弱（P < 0.05），但未被氟烷改变（P > 0.3）。我们得出结论，异氟烷可能增强胞质型PKC介导的血管收缩，而氟烷可能减弱胞质型和膜结合型PKC介导的血管收缩。
