TRPV1 in microvascular regulation

Few studies have described the in vivo role of the capsaicin receptor, TRPV1, in the context of microcirculatory control. Recent in vitro studies have suggested a role for TRPV1 in both the initiation of myogenic tone, and vasodilation; however in vitro experiments may not fully reflect responses seen in vivo . In this study we characterize the microcirculatory response to TRPV1 activation in vivo using the hamster cheek pouch microcirculation. Superfusion of capsaicin, a TRPV1 agonist, results in dose dependent dilation with an EC50 of 31 nM. Superfusion with the TRPV1 antagonist, capsazepine (3x10 −6 M) or acute desensitization of TRPV1 by repeated superfusate application of 10 −6 M capsaicin results in the loss of capsaicin induced vasodilation, but has no influence on myogenic tone. Similarly, chemical dennervation of the cheek pouch (4mg/ml capsaicin injected into the cheek pouch 3 days before experiments) abolishes vasodilator response to capsaicin but has no effect on the development of myogenic tone. Bupivacaine (10 −4 M) does not prevent capsaicin induced vasodilation, suggesting that vasodilation can occur in the absence of neuronal sodium channel activation and afferent nerve conduction. Brief, perivascular micro‐application of capsaicin (10 −5 M) causes local dilation which decays 500–700 μm from the activation site. Repeated capsaicin micro‐application (10 −5 M) results in localized loss of vasodilation at the application site, but preserves capsaicin‐induced vasodilation in upstream or downstream segments of the arteriole and its branches. These data support a role for TRPV1 in arteriolar vasodilation, and do not support a role for TRPV1 in the development of myogenic tone.