Exercise Training Ameliorates Sympathetic Overactivity in Response to Muscle Metaboreflex Stimulation in Spontaneously Hypertensive Rats

Abstract

Aerobic exercise training (ET) improves cardiovascular function during exercise in hypertension. However, the mechanisms underlying these improvements remain largely undetermined. The skeletal muscle metaboreflex is exaggerated in hypertension contributing significantly to altered circulatory control during physical activity. Thus, it is hypothesized that training-induced improvements in cardiovascular function during exercise in hypertension are mediated, in part, by normalization of muscle metaboreflex overactivity. PURPOSE: To investigate the effect of ET on muscle metaboreflex function in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. METHODS: In untrained WKY (WKYUT; n=6), ET WKY (WKYET; n=7; housed in cage with running wheel for 3 months), untrained SHR (SHRUT; n=3) and ET SHR (SHRET; n=7), changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to stimulation of the muscle metaboreflex were assessed. Chemically sensitive afferent fibers were selectively activated by administering the transient receptor potential vanilloid 1 (TRPv1) receptor agonist, capsaicin (0.1, 0.3 and 1.0 μg/100 μl) into the hindlimb arterial supply. TRPv1 is primarily localized to group IV muscle afferent neurons associated with the metaboreflex. RESULTS: As previously reported, the MAP and RSNA responses to capsaicin administration in SHR were significantly greater than WKY. There was no difference between WKYUT and WKYET in the sympathetic responses to metaboreflex activation (0.1μg/100μl: 17±3 vs. 26±7 %; 0.3μg/100μl: 44±16 vs. 52±9 %; 1.0μg/100μl: 47±15 vs. 76±16 %, respectively). Exaggerated RSNA responses to capsaicin administration in SHRUT were attenuated by 3 months of wheel running in SHRET (0.1μg/100μl: 29±11 vs. 20±3 %; 0.3μg/100μl: 88±28 vs. 26±7 %; 1.0μg/100μl: 137±13 vs. 65±18 %, respectively, P<0.05). A similar MAP response profile was likewise produced. CONCLUSIONS: The data demonstrate that ET significantly reduces metaboreflex overactivity in hypertension. This finding suggests that regular physical activity may improve sympathetically-mediated blood pressure regulation during exercise in hypertension, in part, by normalization of metaboreflex function. Supported by NIH HL-088422 and HL-113738