Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation

O'Brien, Fiona, Staunton, Caroline A ORCID: 0000-0003-0647-3063 and Barrett-Jolley, Richard ORCID: 0000-0003-0449-9972 (2022) Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation. BIOLOGY LETTERS, 18 (6). 20220129-.

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Abstract

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 <i>Mus muscularis</i> tail vascular tone and thermoregulation. We measured tail blood flow by pressure plethysmography in lightly sedated <i>M. muscularis</i> (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.

Item Type:	Article
Uncontrolled Keywords:	thermoregulation, tail blood flow, ion channels, non-invasive blood pressure, 3Rs, TRPV4
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	16 Jun 2022 13:43
Last Modified:	18 Jan 2023 20:57
DOI:	10.1098/rsbl.2022.0129
Open Access URL:	https://doi.org/10.1098/rsbl.2022.0129
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3156609