Changes in β-adrenergic receptor-mediated vascular response in the septic rat thoracic aorta

麻醉药或败血症对内皮依赖性血管舒张抑制作用的机制仍有争议。本研究旨在阐明麻醉药或败血症如何干扰内皮介导的血管松弛。挥发性麻醉剂氟烷以浓度依赖性的方式抑制了碳水化合物引起的胞质Ca^<2+>浓度的升高和由此引起的肌肉张力的降低。此外，氟烷浓度以Ca^<2+>依赖的方式部分抑制硝酸甘油诱导的血管松弛。这些结果强烈表明，氟烷干扰内皮介导的血管舒张，无论是在NO合成过程中还是在NO介导的血管舒张过程中。多巴酚丁胺（β1肾上腺素能激动剂）和沙丁胺醇（β2肾上腺素能激动剂）诱导内皮完整血管条的血管松弛。相比之下，多巴酚丁胺在内皮剥脱条中的作用几乎被消除，提示多巴酚丁胺的作用是由内皮介导的。在脓毒症大鼠主动脉中，不仅α-肾上腺素能受体介导的血管收缩受到抑制，β-肾上腺素能受体介导的血管松弛也受到抑制。因此，脓毒症诱导血管舒张的多因子抑制。

The mechanism (s) underlying the inhibitory effect of anesthetics or sepsis on endothelium-dependent vasorelaxation is still controversial. This study intended to clarify how anesthetics or sepsis interfered with endothelium-mediated vasorelaxation.The volatile anesthetic halothane inhibited carbachol-induced increase in cytosolic Ca^<2+> concentration and resultant decrease in muscle tension in aconcentration-dependent manner. In addition,halothane concentration dependently inhibited nitroglycerin-induced vasorelaxation partly in a Ca^<2+>-dependent fashion. These findings strongly indicated that halothane interfered with endothelium-mediated vasorelaxation both at the NO synthetic process and at the NO-mediated vasorelaxing process. Dobutamine, a β1 adrenergic agonist, and salbutamol, a β2 adrenergic agonist, induced vasorelaxation in endothelium-intact vascular strip. In contrast, dobutamine's effect was almost abolished in endothelium-denuded strip, suggesting that dobutamine's effect was mediated by endothelium. Not only α-adrenergic receptor-mediated vasoconstriction, but β-adrenergic receptor-mediated vasorelaxation was inhibited in the septic rat aorta. Therefore, sepsis induces multifactorial inhibition on vascular relaxation.