TRPV1 in arteries enables a rapid myogenic tone.
TRPV1 in arteries enables a rapid myogenic tone.
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DOI：
10.1113/jp281873
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Ahern GP
中科院分区：
文献类型：
--
作者：
Phan TX;Ton HT;Gulyás H;Pórszász R;Tóth A;Russo R;Kay MW;Sahibzada N;Ahern GP
小动脉通过调整其直径以响应局部血压的变化来维持流量。在这个称为肌源性反应的过程中，血管平滑肌机械传感器主要通过改变膜电位来控制张力。一般来说，肌源性反应发生缓慢（分钟）。然而，在心脏和骨骼肌中，张力被迅速激活（数十秒），并通过短暂（100 ms）的动脉收缩而终止。以前，我们发现TRPV 1在供应骨骼肌、心脏和脂肪的小动脉平滑肌中广泛表达。在这里，我们揭示了TRPV 1在这些组织的快速肌源性张力中的关键作用。TRPV 1拮抗剂在体外和体内扩张骨骼肌小动脉，增加离体心脏的冠状动脉流量，并短暂降低血压。所有这些药理作用都被TRPV 1的遗传破坏所消除。分离的血管平滑肌细胞的拉伸或动脉中血管内压力的升高触发了Ca 2+信号传导和血管收缩。这些牵张反应中的大多数是TRPV 1介导的，其余的张力被TRPM 4拮抗剂9-phenantrol抑制。值得注意的是，与TRPV 1缺失小鼠相比，野生型小鼠的动脉张力发展更快。此外，短暂收缩小动脉后立即血管舒张依赖于TRPV 1，与TRPV 1的快速失活一致。药理学实验表明，膜拉伸激活磷脂酶C/蛋白激酶C信号传导结合热激活TRPV 1，并反过来激活L型Ca 2+通道。这些结果表明，TRPV 1在心脏和骨骼肌肌源性张力和血流的动态调节中起着关键作用。TRPV 1作为肌源性张力的转导通道发挥作用。小动脉肌细胞的伸展通过PLC/PKC途径和温度激活TRPV 1。反过来，通过TRPV 1的去极化电流激活L型Ca 2+通道（CaV1.2），触发细胞缩短。此外，TRPV 1能够动态控制张力，如TRPV 1缺陷动脉的实验所揭示的。在动脉拉伸时，在TRPV 1不存在的情况下，血管直径的恢复明显较慢。类似地，短暂收缩后的立即血管舒张也是TRPV 1依赖性的。因此，TRPV 1的快速激活和失活被认为是这些动态变化的基础，有助于骨骼肌和心脏中血流的时间控制。
Arterioles maintain blow flow by adjusting their diameter in response to changes in local blood pressure. In this process called the myogenic response, a vascular smooth muscle mechanosensor controls tone predominantly through altering the membrane potential. In general, myogenic responses occur slowly (minutes). In the heart and skeletal muscle, however, tone is activated rapidly (tens of seconds) and terminated by brief (100 ms) arterial constrictions. Previously, we identified extensive expression of TRPV1 in the smooth muscle of arterioles supplying skeletal muscle, heart and fat. Here we reveal a critical role for TRPV1 in the rapid myogenic tone of these tissues. TRPV1 antagonists dilated skeletal muscle arterioles in vitro and in vivo, increased coronary flow in isolated hearts, and transiently decreased blood pressure. All of these pharmacologic effects were abolished by genetic disruption of TRPV1. Stretch of isolated vascular smooth muscle cells or raised intravascular pressure in arteries triggered Ca2+ signaling and vasoconstriction. The majority of these stretch-responses were TRPV1-mediated, with the remaining tone being inhibited by the TRPM4 antagonist, 9-phenantrol. Notably, tone developed more quickly in arteries from wild-type compared with TRPV1-null mice. Furthermore, the immediate vasodilation following brief constriction of arterioles depended on TRPV1, consistent with a rapid deactivation of TRPV1. Pharmacologic experiments revealed that membrane stretch activates phospholipase C/protein kinase C signaling combined with heat to activate TRPV1, and in turn, L-type Ca2+ channels. These results suggest a critical role, for TRPV1 in the dynamic regulation of myogenic tone and blood flow in the heart and skeletal muscle. TRPV1 functions as a transduction channel for myogenic tone. Stretch of arteriolar myocytes activates TRPV1 via a PLC/PKC pathway and temperature. In turn, the depolarizing current through TRPV1 activates the L-type Ca2+ channel (CaV1.2) to trigger cell shortening. Moreover, TRPV1 enables dynamic control of tone as revealed by experiments with TRPV1-deficient arteries. Upon arterial stretch the restoration of vessel diameter is significantly slower in the absence of TRPV1. Similarly, the immediate vasodilation following a brief constriction is also TRPV1 dependent. Thus, rapid activation and deactivation of TRPV1 is proposed to underlie these dynamic changes, contributing to the temporal control of blood flow in skeletal muscle and the heart.
DOI：
10.1111/micc.12025
发表时间：
2013-04
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Mauban JR;Zacharia J;Zhang J;Wier WG
通讯作者：
Wier WG