Functions of sensory TRP channels in vascular responses to chemical and thermal stimuli

Regulation of the blood pressure is an essential physiological process mainly regulated by the vascular tone that is dependent on the function of multiple ion channels that determine the dynamics of intracellular Ca2+concentration in vascular smooth muscle cells, endothelial cells, as well as in perivascular nerves. Recent studies indicate that sensory transient receptor potential channels expressed in perivascular nerves may be implicated in the mechanisms underlying arterial pressure regulationthrough the release of many factors such as CGRP and NA due to their capacity to influence cellular excitability and intracellular Ca2+signaling. The vascular function of these channels has been associated to their chemosensory and thermosensory properties, but their actual relevance to blood pressure regulation remain fully unknown. Within the TRPM family, the role of TRPM3 channels in the contribution to vascular tone in resistance arteries has not been yet stablished. Therefore, using anatomical localization by immunofluorescence microscopy and patch-clamp recordings in isolated VSMC, we found that TRPM3 expression in mesenteric arteries is restricted to perivascular sensory nerves. Pressure myography experiments showed that chemical activation of TRPM3 channels in mesenteric arteries leads to vasodilatation, via CGRP release from perivascular sensory nerves. It has also been reported that sensory TRP channels also modulate the vascular function due to their involvement in sensing environmental stimuli, being actual sensor of thermal challenges. Thus, we examine the roles of sensory TRP channels in a local vascular response to low temperatures and we found thatcold response is mediated by both vasodilatory and a more potent vasoconstrictor mechanisms via the activation of TRPA1 and TRPM8 channels. We concluded that several sensory TRP channels play essential roles in the regulation of vascular tone in response to chemical and thermal challenges.status: publishe