Department of Anesthesiology, Critical Care Section, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA.
Can J Physiol Pharmacol. 2010 Jan;88(1):1-8. doi: 10.1139/Y09-092.
Calcium is the major intracellular messenger that triggers smooth muscle contraction. The study of calcium-binding proteins, such as calmodulin and its downstream effectors, reveals critical regulation of smooth muscle contraction by protein kinases and phosphatases. Moreover, the small GTP-binding protein RhoA and its downstream effector protein, Rho-kinase, have been shown to play a novel role in the regulation of smooth muscle contraction. Studies have shown that the activation of Rho-kinase is involved in the development of endothelial dysfunction, inflammation, restenosis, and increased vascular tone in a number of cardiovascular disorders. Because inhibitors of this pathway promote vasodilation independent of the mechanism that increases vasoconstrictor tone, it is our hypothesis that Rho-kinase is constitutively active in regulating vasoconstrictor tone in the pulmonary and systemic vascular beds. Studies in the literature suggest that the RhoA/Rho-kinase pathway has an important role in the pathogenesis of pulmonary hypertension.
钙是触发平滑肌收缩的主要细胞内信使。钙结合蛋白（如钙调蛋白及其下游效应物）的研究揭示了蛋白激酶和磷酸酶对平滑肌收缩的关键调节作用。此外，小 GTP 结合蛋白 RhoA 及其下游效应蛋白 Rho-kinase 已被证明在调节平滑肌收缩中发挥新的作用。研究表明，Rho-kinase 的激活参与了多种心血管疾病中内皮功能障碍、炎症、再狭窄和血管张力增加的发展。由于该途径的抑制剂通过增加血管收缩剂张力的机制促进血管舒张，因此我们假设 Rho-kinase 在调节肺血管和全身血管床的血管收缩剂张力方面持续活跃。文献中的研究表明，RhoA/Rho-kinase 途径在肺动脉高压的发病机制中具有重要作用。
