Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation.
Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation.
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DOI：
10.1098/rsbl.2022.0129
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发表时间：
2022-06
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
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在人类中，皮肤是主要的体温调节器官，血管扩张导致身体快速降温，而在啮齿目动物中，尾巴发挥着类似的功能。可能涉及许多热检测机制，包括瞬时受体电位香草型4(TRPV4)，一种具有热敏特性的离子通道。以前的研究表明，TRPV4是一种局部作用于血管的血管扩张剂，因此，我们在这里研究了结构性TRPV4活性是否影响小鼠肌肉尾部血管张力和体温调节。我们在一定的环境温度范围内，通过压力体积描记术测量了轻度镇静的肌肉分枝杆菌(CD1株)的尾部血流量，并在有和没有通过血脑屏障的TRPV4拮抗剂GSK2193874的情况下进行了腹膜内注射。我们还测量了心率和血压。正如预期的那样，对于体温调节器官，我们发现尾部血流量随着温度的升高而增加。然而，出乎意料的是，我们发现GSK2193874在所有温度下都增加了尾部血流量，我们观察到了心率变异性的变化。由于局部激活TRPV4会导致血管扩张，从而增加尾部血流量，这些数据表明，TRPV4拮抗剂导致的尾部血流量增加可能来自血管本身以外的某个部位，可能是在中央心血管控制中心。
In humans, skin is a primary thermoregulatory organ, with vasodilation leading to rapid body cooling, whereas in Rodentia the tail performs an analogous function. Many thermodetection mechanisms are likely to be involved including transient receptor potential vanilloid-type 4 (TRPV4), an ion channel with thermosensitive properties. Previous studies have shown that TRPV4 is a vasodilator by local action in blood vessels, so here, we investigated whether constitutive TRPV4 activity affects Mus muscularis tail vascular tone and thermoregulation. We measured tail blood flow by pressure plethysmography in lightly sedated M. muscularis (CD1 strain) at a range of ambient temperatures, with and without intraperitoneal administration of the blood–brain barrier crossing TRPV4 antagonist GSK2193874. We also measured heart rate (HR) and blood pressure. As expected for a thermoregulatory organ, we found that tail blood flow increased with temperature. However, unexpectedly, we found that GSK2193874 increased tail blood flow at all temperatures, and we observed changes in HR variability. Since local TRPV4 activation causes vasodilation that would increase tail blood flow, these data suggest that increases in tail blood flow resulting from the TRPV4 antagonist may arise from a site other than the blood vessels themselves, perhaps in central cardiovascular control centres.
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影响因子：
4
作者：
Feetham CH;O'Brien F;Barrett-Jolley R
通讯作者：
Barrett-Jolley R
DOI：
10.1007/bf00684671
发表时间：
1985-01-01
影响因子：
2
作者：
CONLEY, KE;PORTER, WP
通讯作者：
PORTER, WP
影响因子：
4
作者：
Kim JW;Seok HS;Shin H
通讯作者：
Shin H
DOI：
10.1096/fj.15-272526
发表时间：
2015-10
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Alawi KM;Aubdool AA;Liang L;Wilde E;Vepa A;Psefteli MP;Brain SD;Keeble JE
通讯作者：
Keeble JE
影响因子：
4.8
作者：
Chung, MK;Lee, H;Caterina, MJ
通讯作者：
Caterina, MJ