Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature
Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature
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DOI：
10.1111/apha.12355
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发表时间：
2015-02-01
影响因子：
6.3
通讯作者：
Gollasch, M.
中科院分区：
文献类型：
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作者：
Chen, L.;Kassmann, M.;Gollasch, M.
目的瞬时受体电位香草酸1（TRPV 1）和香草酸4（TRPV 4）阳离子通道最近被发现可促进小鼠肠系膜动脉内皮依赖性舒张。然而，TRPV 1和TRPV 4在肾血管系统中的作用在很大程度上是未知的。我们假设，TRPV 1/4发挥作用，在内皮依赖性血管舒张的肾vascular.MethodsWe研究了功能TRPV 1/4的分布沿沿着不同节段的肾血管。以肠系膜动脉作为对照血管进行研究。结果TRPV 1激动剂辣椒素可松弛小鼠肠系膜动脉，EC 50为25 nm，但大型小鼠肾动脉或大鼠降直血管仅在浓度高出100倍时才能松弛。辣椒素在低纳摩尔浓度范围内的血管舒张作用是内皮依赖性的，并且在Trpv 1-/-小鼠的血管中不存在。TRPV 4激动剂GSK 1016790 A舒张大的肾动脉、肠系膜动脉和直血管，EC 50分别为18、63和10 nm。这些作用是内皮依赖性的，并被TRPV 4拮抗剂AB 159908（10 m）抑制。辣椒素和GSK 1016790 A在离体小鼠灌流肾中产生血管扩张，EC 50分别为23和3 nm。辣椒素的影响在很大程度上减少在Trpv 1-/-肾脏，和GSK 1016790 A的影响被抑制在Trpv 4-/- kidneys.ConclusionOur结果表明，两个TRPV通道具有独特的网站的血管调节功能在肾脏与功能TRPV 1具有狭窄的，离散的分布在阻力血管和TRPV 4具有更普遍的，广泛的分布沿着不同的血管段。我们认为TRPV 1/4通道是肾脏部位特异性血管舒张的有效治疗靶点。
AimTransient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels.MethodsWe studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels.ResultsThe TRPV1 agonist capsaicin relaxed mouse mesenteric arteries with an EC50 of 25nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist GSK1016790A relaxed large conducting renal arteries, mesenteric arteries and vasa recta with EC50 of 18, 63nm and 10nm respectively. These effects were endothelium-dependent and inhibited by a TRPV4 antagonist, AB159908 (10m). Capsaicin and GSK1016790A produced vascular dilation in isolated mouse perfused kidneys with EC50 of 23 and 3nm respectively. The capsaicin effects were largely reduced in Trpv1 -/- kidneys, and the effects of GSK1016790A were inhibited in Trpv4 -/- kidneys.ConclusionOur results demonstrate that two TRPV channels have unique sites of vasoregulatory function in the kidney with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney.