Key result
Intraperitoneal administration of the TRPV4 antagonist GSK2193874 unexpectedly increased tail blood flow at all ambient temperatures and altered heart rate variability in a mouse model.
Why the study?
Previous studies showed TRPV4 causes local vasodilation, prompting investigation into whether constitutive TRPV4 activity affects Mus muscularis tail vascular tone and thermoregulation.
Does intraperitoneal administration of the TRPV4 antagonist GSK2193874 affect tail blood flow and thermoregulation in lightly sedated Mus muscularis mice?
Does intraperitoneal administration of the TRPV4 antagonist GSK2193874 affect tail blood flow and thermoregulation in lightly sedated Mus muscularis mice?
Systemic TRPV4 antagonism increases tail blood flow in mice, suggesting a central rather than local vascular mechanism for thermoregulation.
Unexpected tail vasodilation with TRPV4 blockade in mice should not change practice; leaves open central thermoregulatory mechanisms for research.
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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O’Brien et al. (2022) studied Thermoregulation (mouse model). GSK2193874 vs. without administration was evaluated on Tail blood flow. Intraperitoneal administration of the TRPV4 antagonist GSK2193874 unexpectedly increased tail blood flow at all ambient temperatures and altered heart rate variability in a mouse model.
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