Systemic application of the TRPV4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation
In humans the skin is a primary thermoregulatory organ, with vasodilation leading to rapid body cooling, whereas in rodents the tail performs an analogous function. TRPV4 is a widely distributed ion channel with both mechanical and thermosensitive properties. Previous studies have shown that TRPV4 can act as vasodilator by local action in blood vessels, and in this study we investigated whether there was a constitutive role for TRPV4 in mouse tail vascular tone and thermoregulation. We measured tail blood flow by pressure plethysmography in lightly sedated mice 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 with and without GSK2193874. As predicted, we found that tail blood flow increased with temperature. However, unexpectedly we found that the TRPV4 antagonist GSK2193874 increased tail blood flow at all temperatures. There were few detectable differences in heart rate, blood pressure or short-range heart rate variability. Since arterial TRPV4 activation is known to cause vasodilation that would increase tail blood flow, these data suggest that increases in tail blood flow resulting from the TRPV4 antagonist must arise from a site other than the blood vessels themselves, perhaps in central cardiovascular control centres such as the paraventricular nucleus of the hypothalamus.