Systemic application of the TRPV4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation

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 effects Mus muscularis tail vascular tone and thermoregulation. We measured tail blood flow by pressure plethysmography in lightly sedated Mus 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 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 heart rate 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.

Methods
CODA Non-invasive tail cuff.