Mechanisms of inhibition by volatile anesthetics on beta-adrenoceptor-mediated relaxation in the vascular smooth muscle

这项研究旨在确定挥发性麻醉剂氟烷和异氟醚是否抑制β-肾上腺素受体介导的反应，如果抑制，哪些信号转导步骤是重要的。我们发现，在临床相关浓度下使用的挥发性麻醉剂可以干扰由β-肾上腺素能受体激动剂异丙肾上腺素介导的反应。氟烷和异氟醚可抑制异丙肾上腺素引起的血管扩张和胞浆内钙离子浓度的下降，而对腺苷环化酶激动剂Forsklin和膜通透性cAMP dBcAMP引起的血管扩张影响不大。这一结果与另一结果一致，即两种麻醉剂均可抑制异丙肾上腺素引起的环磷酸腺苷含量增加，但不影响Forsklin诱导的环磷酸腺苷含量增加。此外，两种试剂都不干扰β-肾上腺素能受体的配基结合特性。这些结果表明，氟烷和异氟烷主要干扰位于β-肾上腺素能受体和腺苷环化酶之间的β-肾上腺素能受体介导的反应；因此，合乎逻辑的位置应该包括G蛋白。除了由β-肾上腺素能受体-环状AMP系统介导的血管松弛外，我们还研究了氟烷对一氧化氮(NO)-环状GMP系统介导的血管松弛的影响。我们用硝酸甘油作为NO供体。我们发现氟烷以浓度依赖的方式干扰硝酸甘油诱导的血管松弛。此外，氟烷的抑制作用受[Ca^&lt；2&gt；]i依赖和[Ca^&lt；2&gt；]i非依赖两种机制的控制。

This study was designed to determine whether the volatile anesthetics halothane and isoflurane inhibit beta-adrenoceptor-mediated responses, and which signal transduction steps are important for the inhibition if they do. We found that the volatile anesthetics used at clinically relevant concentrations can interfere with responses mediated by the beta-adrenoceptor agonist, isoproterenol. Halothane and isoflurane impaired isoproterenol-induced vasodilation and a decline of cytosolic concentrations of Ca^<2+> ([Ca^<2+>]i), whereas they only slightly affected vasodilation induced by the adenylyl cyclase activator, forskolin, and the membrane-permeable cyclic AMP, dbcAMP.This finding is consistent with the additional result that both anesthetics inhibited isoproterenol-induced, but not forskolin-induced, increases in cyclic AMP contents. Furthermore, both agents did not interfere with the ligand-binding property to the beta-adrenoceptor. These results indicate that halothane and isoflurane predominantly interfere with beta-adrenoceptor-mediated responses at the step between the beta-adrenoceptor and adenylyl cyclase ; the logical site would therefore include Gproteins.In addition to the vasorelaxation mediated by the beta-adrenoceptor-cyclic AMP system, we also investigated the effect of halothane on the vasorelaxation mediated by the nitric oxide (NO)-cyclic GMP system. We used nitroglycerin as a NO donor. We found that halothane interfered with nitroglycerin-induced vasorelaxation in a concentration-dependent fashion. Furthermore, halothane's inhibition was govemed by both [Ca^<2+>]i-dependent and [Ca^<2+>]i-independent mechanisms.