Yang Qunhui, Hori Masatoshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Life (Basel). 2021 Jul 16;11(7):702. doi: 10.3390/life11070702.
Hypertension is a key risk factor for cardiovascular disease and it is a growing public health problem worldwide. The pathophysiological mechanisms of vascular smooth muscle (VSM) contraction contribute to the development of hypertension. Calcium (Ca)-dependent and -independent signaling mechanisms regulate the balance of the myosin light chain kinase and myosin light chain phosphatase to induce myosin phosphorylation, which activates VSM contraction to control blood pressure (BP). Here, we discuss the mechanism of the contractile machinery in VSM, especially RhoA/Rho kinase and PKC/CPI-17 of Ca sensitization pathway in hypertension. The two signaling pathways affect BP in physiological and pathophysiological conditions and are highlighted in pulmonary, pregnancy, and salt-sensitive hypertension.
高血压是心血管疾病的关键危险因素,且在全球范围内是一个日益严重的公共卫生问题。血管平滑肌(VSM)收缩的病理生理机制促成了高血压的发展。钙(Ca)依赖性和非依赖性信号机制调节肌球蛋白轻链激酶和肌球蛋白轻链磷酸酶的平衡,以诱导肌球蛋白磷酸化,从而激活VSM收缩来控制血压(BP)。在此,我们讨论VSM中收缩机制,尤其是高血压中钙敏化途径的RhoA/Rho激酶和PKC/CPI-17。这两条信号通路在生理和病理生理条件下均影响血压,并且在肺性高血压、妊娠高血压和盐敏感性高血压中尤为突出。