TRPV1 in microvascular regulation

Abstract

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 (3x10−6M) 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 (10−5M) 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.