Skeletal muscle metaboreflex overactivity is mediated by the TRPv1 receptor in spontaneously hypertensive rats

Evidence suggests the skeletal muscle metaboreflex (SMM) is overactive in hypertension contributing to the exaggerated cardiovascular response to exercise in this disease. However, the mechanism underlying SMM overactivity remains undetermined. In normotensive rats, stimulation of the transient receptor potential vanilloid 1 (TRPv1) receptor, primarily localized to group IV afferent neurons associated with the SMM, has been shown to contribute to the circulatory response to exercise. Thus, we hypothesized that the TRPv1 receptor mediates the enhanced SMM activity manifest in hypertension. To test this hypothesis, the SMM was supra‐stimulated by electrically inducing hindlimb muscle contraction during circulatory occlusion of the limb in decerebrate normotensive Wistar‐Kyoto (WKY, n = 12) and spontaneously hypertensive (SHR, n = 12) rats. Supra‐stimulation of the SMM evoked significantly larger increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in SHR compared to WKY. Local administration of the TRPv1 receptor antagonist capsazepine significantly attenuated these responses in both groups. However, the magnitudes of the capsazepine‐induced reductions in MAP and RSNA were significantly greater in SHR compared to WKY. The results suggest that SMM overactivity in hypertension is mediated, in part, by stimulation of the TRPv1 receptor. Supported by NIH HL‐088422