RhoA/Rho-kinase, vascular changes, and hypertension.
RhoA/Rho-kinase, vascular changes, and hypertension.
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DOI：
10.1007/s11906-001-0028-4
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发表时间：
2001-04-01
影响因子：
5.6
通讯作者：
Webb, R C
中科院分区：
文献类型：
--
作者：
Chitaley, K;Weber, D;Webb, R C
高血压是血管外周阻力持续增加的结果，部分原因是血管重塑和血管收缩剂敏感性增加。通过各种收缩激动剂刺激异源三聚体G蛋白偶联受体激活胞内信号分子，导致胞质Ca++增加，随后通过Ca++/钙调蛋白依赖性肌球蛋白轻链激酶磷酸化肌球蛋白轻链。此外，一部分α-肾上腺素能、肾上腺素能和内皮素-1诱导的收缩部分由小G蛋白RhoA和下游靶点Rho激酶的钙非依赖性激活介导。来自高血压动物的离体动脉已经显示出对各种激动剂的收缩敏感性增加，并表现出重塑的证据。最近的数据表明，这些血管变化中的一些可能是由RhoA/Rho激酶活性增加介导的，这可能为高血压的治疗引入一种新的治疗方法。
Hypertension, the result of a sustained increase in vascular peripheral resistance, is partly due to vascular remodeling and increased vasoconstrictor sensitivity. Stimulation of heterotrimeric G-protein-coupled receptors by various contractile agonists activates intracellular signaling molecules to result in an increase in cytosolic Ca++ and the subsequent phosphorylation of myosin light chain by Ca++/calmodulin-dependent myosin light chain kinase. Additionally, a portion of alpha-adrenergic, serotonergic, and endothelin-1-induced contraction is partially mediated by the calcium-independent activation of the small G-protein RhoA and of a downstream target, Rho-kinase. Isolated arteries from hypertensive animals have been shown to have an increased contractile sensitivity to various agonists and to exhibit evidence of remodeling. Recent data suggest that some of these vascular changes may be mediated by increased activity of RhoA/Rho-kinase, potentially introducing a novel therapeutic approach for the treatment of hypertension.