TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure
TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure
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DOI：
10.1152/ajpheart.00241.2009
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发表时间：
2009-09-01
影响因子：
4.8
通讯作者：
Brayden, Joseph E.
中科院分区：
文献类型：
--
作者：
Earley, Scott;Pauyo, Thierry;Brayden, Joseph E.
Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden JE。trpv4依赖性外周阻力动脉扩张影响动脉压。[J] .中国生物医学工程学报，2009,31(2):393 - 398。首次发表于2009年7月17日；doi: 10.1152 / ajpheart.00241.2009。瞬时受体电位香草样蛋白4 （TRPV4）通道被认为是内皮细胞和血管平滑肌细胞钙内流的介质，也是血管张力的潜在重要调节剂。然而，对于TRPV4在阻力血管系统中的功能作用以及这些通道如何影响血流动力学特性知之甚少。在本研究中，我们使用TRPV4敲除（KO）小鼠检测了体外动脉血管舒缩活性，并记录了体内血压动态。与野生型（WT）小鼠相比，TRPV4 KO小鼠肠系膜抵抗动脉中乙酰胆碱诱导的超极化和血管舒张减少了75%。此外，11,12-环氧二碳三烯酸（EET），一种被认为是内皮衍生的超极化因子，激活trpv4样阳离子电流并使血管平滑肌细胞膜超极化，导致WT小鼠肠系膜动脉扩张。相比之下，11,12- eet对TRPV4 KO小鼠肠系膜动脉的膜电位、直径或离子电流没有影响。内皮的破坏使11,12- eet诱导的超极化和血管舒张减少了50%。内皮细胞（小电导和中等电导）或平滑肌细胞（大电导）K+通道被阻断后，这些反应也被类似地抑制，这表明内皮细胞和平滑肌细胞中的11,12- eet活性、TRPV4和K+通道之间存在联系。最后，我们发现，与WT小鼠相比，TRPV4 KO中一氧化氮合酶抑制引起的高血压更大。这些结果支持了内皮和平滑肌TRPV4通道在响应内皮源性因子的肠系膜动脉血管舒张中起关键作用的结论，并提示在体内这种机制与高血压刺激的作用相反。
Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden JE. TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol Heart Circ Physiol 297: H1096-H1102, 2009. First published July 17, 2009; doi: 10.1152/ajpheart.00241.2009. Transient receptor potential vanilloid 4 (TRPV4) channels have been implicated as mediators of calcium influx in both endothelial and vascular smooth muscle cells and are potentially important modulators of vascular tone. However, very little is known about the functional roles of TRPV4 in the resistance vasculature or how these channels influence hemodynamic properties. In the present study, we examined arterial vasomotor activity in vitro and recorded blood pressure dynamics in vivo using TRPV4 knockout (KO) mice. Acetylcholine-induced hyperpolarization and vasodilation were reduced by similar to 75% in mesenteric resistance arteries from TRPV4 KO versus wild-type (WT) mice. Furthermore, 11,12-epoxyeicosatrienoic acid (EET), a putative endothelium-derived hyperpolarizing factor, activated a TRPV4-like cation current and hyperpolarized the membrane of vascular smooth muscle cells, resulting in the dilation of mesenteric arteries from WT mice. In contrast, 11,12-EET had no effect on membrane potential, diameter, or ionic currents in the mesenteric arteries from TRPV4 KO mice. A disruption of the endothelium reduced 11,12-EET-induced hyperpolarization and vasodilatation by similar to 50%. A similar inhibition of these responses was observed following the block of endothelial (small and intermediate conductance) or smooth muscle (large conductance) K+ channels, suggesting a link between 11,12-EET activity, TRPV4, and K+ channels in endothelial and smooth muscle cells. Finally, we found that hypertension induced by the inhibition of nitric oxide synthase was greater in TRPV4 KO compared with WT mice. These results support the conclusion that both endothelial and smooth muscle TRPV4 channels are critically involved in the vasodilation of mesenteric arteries in response to endothelial-derived factors and suggest that in vivo this mechanism opposes the effects of hypertensive stimuli.