Cox Robert H, Rusch Nancy J
Lankenau Institute for Medical Research, Jefferson Health System, Philadelphia, PA, USA.
Microcirculation. 2002;9(4):243-57. doi: 10.1038/sj.mn.7800140.
The diameters of small arteries and arterioles are tightly regulated by the dynamic interaction between Ca(2+) and K(+) channels in the vascular smooth muscle cells. Calcium influx through voltage-gated Ca(2+) channels induces vasoconstriction, whereas the opening of K(+) channels mediates hyperpolarization, inactivation of voltage-gated Ca(2+) channels, and vasodilation. Three types of voltage-sensitive ion channels have been highly implicated in the regulation of resting vascular tone. These include the L-type Ca(2+) (Ca(L)) channels, voltage-gated K(+) (K(V)) channels, and high-conductance voltage- and Ca(2+)-sensitive K(+) (BK(Ca)) channels. Recently, abnormal expression profiles of these ion channels have been identified as part of the pathogenesis of arterial hypertension and other vasospastic diseases. An increasing number of studies suggest that high blood pressure may trigger cellular signaling cascades that dynamically alter the expression profile of arterial ion channels to further modify vascular tone. This article will briefly review the properties of Ca(L), K(V), and BK(Ca) channels, present evidence that their expression profile is altered during systemic hypertension, and suggest potential mechanisms by which the signal of elevated blood pressure may result in altered ion channel expression. A final section will discuss emerging concepts and opportunities for the development of new vasoactive drugs, which may rely on targeting disease-specific changes in ion channel expression as a mechanism to lower vascular tone during hypertensive diseases.
小动脉和微动脉的直径受到血管平滑肌细胞中钙（Ca(2+)）通道和钾（K(+)）通道之间动态相互作用的严格调控。通过电压门控钙（Ca(2+)）通道的钙内流会诱导血管收缩，而钾（K(+)）通道的开放则介导超极化、电压门控钙（Ca(2+)）通道的失活以及血管舒张。三种类型的电压敏感性离子通道与静息血管张力的调节密切相关。这些通道包括L型钙（Ca(L)）通道、电压门控钾（K(V)）通道和高电导电压及钙敏感钾（BK(Ca)）通道。最近，这些离子通道的异常表达谱已被确定为动脉高血压和其他血管痉挛性疾病发病机制的一部分。越来越多的研究表明，高血压可能触发细胞信号级联反应，动态改变动脉离子通道的表达谱，从而进一步改变血管张力。本文将简要回顾Ca(L)、K(V)和BK(Ca)通道的特性，提供证据证明它们的表达谱在系统性高血压期间会发生改变，并提出血压升高信号可能导致离子通道表达改变的潜在机制。最后一部分将讨论新血管活性药物开发的新兴概念和机会，这些药物可能依赖于靶向离子通道表达的疾病特异性变化，作为在高血压疾病期间降低血管张力的一种机制。
