Fisher S A
University of Maryland School of Medicine, Baltimore, MD, United States.
Adv Pharmacol. 2017;78:383-415. doi: 10.1016/bs.apha.2016.07.003. Epub 2016 Oct 14.
At its simplest resistance to blood flow is regulated by changes in the state of contraction of the vascular smooth muscle (VSM), a function of the competing activities of the myosin kinase and phosphatase determining the phosphorylation and activity of the myosin ATPase motor protein. In contrast, the vascular system of humans and other mammals is incredibly complex and highly regulated. Much of this complexity derives from phenotypic diversity within the smooth muscle, reflected in very differing power outputs and responses to signaling pathways that regulate vessel tone, presumably having evolved over the millennia to optimize vascular function and its control. The highly regulated nature of VSM tone, described as pharmacomechanical coupling, likely underlies the many classes of drugs in clinical use to alter vascular tone through activation or inhibition of these signaling pathways. This review will first describe the phenotypic diversity within VSM, followed by presentation of specific examples of how molecular diversity in signaling, myofilament, and calcium cycling proteins impacts arterial smooth muscle function and drug responses.
最简单地说，血流阻力是由血管平滑肌（VSM）收缩状态的变化来调节的，这是肌球蛋白激酶和磷酸酶竞争活动的结果，它们决定了肌球蛋白ATPase运动蛋白的磷酸化和活性。相比之下，人类和其他哺乳动物的血管系统极其复杂且受到高度调节。这种复杂性很大程度上源于平滑肌内的表型多样性，表现为功率输出和对调节血管张力的信号通路的反应差异很大，推测这是在数千年的进化过程中为优化血管功能及其控制而形成的。VSM张力的高度调节特性，即药物机械偶联，可能是临床使用的许多类药物通过激活或抑制这些信号通路来改变血管张力的基础。本综述将首先描述VSM内的表型多样性，然后列举具体例子说明信号、肌丝和钙循环蛋白中的分子多样性如何影响动脉平滑肌功能和药物反应。
