Transient receptor potential vanilloid 4 (TRPV4) channels exist on vascular endothelial cells and eccrine sweat gland secretory cells in human skin. Here, we assessed if TRPV4 channels contribute to cutaneous vasodilation and sweating during whole-body passive heat stress (protocol 1) and to cutaneous vasodilation during post-occlusive reactive hyperemia and local thermal hyperemia (protocol 2). Intradermal microdialysis was employed to locally deliver pharmacological agents to forearm skin sites where cutaneous vascular conductance (CVC) and sweat rate were assessed. In protocol 1 (twelve young adults), CVC and sweat rate were increased by passive whole-body heating resulting in a body core temperature elevation of 1.2±0.1ºC. The elevated CVC and sweat rate assessed at sites treated with TRPV4 channel antagonist (either 200 µM HC-067047 or 125 µM GSK2193874) were not different from the vehicle control site (5 % dimethyl sulfoxide). After whole-body heating, a TRPV4 channel agonist (100 µM GSK1016790A) was administered to each skin site, eliciting elevations in CVC. Relative to control, this response was partly attenuated by both TRPV4 channel antagonists, confirming drug efficacy. In protocol 2 (ten young adults), CVC was increased following a 5-min arterial occlusion and during local heating from 33 to 42ºC. These responses did not differ between the control and the TRPV4 channel antagonist sites (200 µM HC-067047). We show that TRPV4 channels are not required for regulating cutaneous vasodilation or sweating during a whole-body passive heat stress. Further, they are not required for regulating cutaneous vasodilation during post-occlusive reactive hyperemia and local thermal hyperemia.

中文翻译：

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TRPV4通道阻滞不会调节热疗期间或皮肤闭塞后反应性和热性充血的皮肤血管舒张和出汗

瞬态受体电位类香草酸4（TRPV4）通道存在于人皮肤的血管内皮细胞和内分泌汗腺分泌细胞上。在这里，我们评估了TRPV4通道是否在全身被动热应激（协议1）期间促成皮肤血管舒张和出汗，在闭塞后反应性充血和局部热血过多（协议2）期间是否促成皮肤血管舒张。皮内微透析用于将药理剂局部递送至前臂皮肤部位，在该部位评估皮肤血管电导（CVC）和出汗率。在方案1（十二个年轻人）中，被动全身加热会增加CVC和出汗率，从而使身体核心温度升高1.2±0.1ºC。在用TRPV4通道拮抗剂治疗的部位（200 µM HC-067047或125 µM GSK2193874）评估的CVC和出汗率升高与媒介物对照部位（5％二甲基亚砜）没有差异。全身加热后，将TRPV4通道激动剂（100 µM GSK1016790A）施用到每个皮肤部位，引起CVC升高。相对于对照，该反应被两种TRPV4通道拮抗剂部分减弱，从而证实了药物疗效。在方案2中（十个年轻人），在5分钟的动脉闭塞后以及从33至42ºC的局部加热期间，CVC升高。这些反应在对照和TRPV4通道拮抗剂位点（200 µM HC-067047）之间没有差异。我们显示，TRPV4通道在全身被动热应激过程中不需要调节皮肤血管舒张或出汗。进一步，