Development ofnew drugs for the treatment of the septic shock

血管扩张性感染性休克是由于血管平滑肌过度松弛和对内源性血管收缩药敏感性降低所致。肌球蛋白磷酸化导致肌肉收缩，而肌球蛋白磷酸酶引起的肌球蛋白去磷酸化与肌肉松弛有关。在这项研究中，我们研究了肌球蛋白磷酸酶抑制剂在一氧化氮供体硝普钠存在的情况下对大鼠主动脉环血管收缩的调节作用。肌球蛋白磷酸酶抑制剂具有剂量依赖性的血管收缩作用。硝普钠对血管的收缩作用不减弱。然而，在活体大鼠模型中，静脉注射肌球蛋白磷酸酶抑制剂没有表现出任何血流动力学变化。

Vasodilatory septic shock is resulted from excessive vascular smooth muscle relaxation and decreased sensitivity to endogenous vasoconstrictors. Myosin phosphorylation induces smooth muscle contraction, and myosin dephosphorylation, which is occurred by myosin phosphatase, is related to muscle relaxation. In this study, we investigated whether myosin phosphatase inhibitor regulated vascular smooth muscle contraction even though presenting of sodium nitroprusside, nitric oxide donor, in aortic ring of the rats. Myosin phosphatase inhibitor had an effect of vasoconstriction in the dose dependent manner. The vasoconstriction effects were not attenuated by sodium nitroprusside. However, in vivo rat model, intravenous administration of myosin phosphatase inhibitor did not show any hemodynamic changes.