Kawano Yoji, Yoshimura Takeshi, Kaibuchi Kozo
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Japan.
Nagoya J Med Sci. 2002 May;65(1-2):1-8.
Abnormal contraction of vascular smooth muscle contributes to a variety of diseases such as hypertension and vasospasm in coronary and cerebral arteries. An increment in a cytoplasmic Ca2+ concentration is the key event in smooth muscle contraction. However, smooth muscle contraction is modified upon the stimulation by agonists as well as in some pathophysiological situations in Ca(2+)-independent mechanism. The molecular mechanism underlying this modulation was not elucidated. Recent studies have shown the important role of small GTPase Rho and its effector, Rho-associated kinase (Rho-kinase)/ROK/ROCK in Ca(2+)-independent regulation of smooth muscle contraction. The Rho/Rho-kinase pathway modulates the phosphorylation level of myosin light chain (MLC) of myosin II, mainly through the inhibition of myosin phosphatase, and contributes to the agonist-induced Ca(2+)-sensitization in smooth muscle contraction. The Rho/Rho-kinase pathway is involved in the pathogenesis of hypertension, vasospasm and arteriosclerosis, and is a potent target of new therapies for these diseases.
血管平滑肌的异常收缩会导致多种疾病，如高血压以及冠状动脉和脑动脉的血管痉挛。细胞质Ca2+浓度的升高是平滑肌收缩的关键事件。然而，在激动剂刺激以及某些病理生理情况下，平滑肌收缩会通过Ca(2+)非依赖机制发生改变。这种调节的分子机制尚未阐明。最近的研究表明，小GTPase Rho及其效应器Rho相关激酶（Rho激酶）/ROK/ROCK在平滑肌收缩的Ca(2+)非依赖调节中起重要作用。Rho/Rho激酶途径主要通过抑制肌球蛋白磷酸酶来调节肌球蛋白II的肌球蛋白轻链（MLC）的磷酸化水平，并有助于激动剂诱导的平滑肌收缩中的Ca(2+)敏感性增加。Rho/Rho激酶途径参与高血压、血管痉挛和动脉硬化的发病机制，并且是这些疾病新疗法的有效靶点。
