Skeletal muscle reflex-mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats

Mizuno M, Murphy MN, Mitchell JH, Smith SA. Skeletal muscle reflex-mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 300: H968-H977, 2011. First published January 7, 2011; doi: 10.1152/ajpheart.01145.2010.-In hypertension, the blood pressure response to exercise is exaggerated. We demonstrated previously that this heightened pressor response to physical activity is mediated by an overactive skeletal muscle exercise pressor reflex (EPR), with important contributions from its metaboreflex and mechanoreflex components. However, the mechanisms driving the abnormal blood pressure response to EPR activation are largely unknown. Recent evidence in humans suggests that the muscle metaboreflex partially mediates the enhanced EPR-induced pressor response via abnormally large changes in sympathetic nerve activity (SNA). Whether the muscle mechanoreflex induces similarly exaggerated alterations in SNA in hypertension remains unknown, as does the role of the mechanoreceptors mediating muscle reflex activity. To address these issues, the EPR was selectively activated by electrically inducing hindlimb muscle contraction in decerebrate normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Stimulation of the EPR evoked significantly larger increases in mean arterial pressure (MAP) and renal SNA (RSNA) in SHR compared with WKY (Delta RSNA from baseline: 140 +/- 11 vs. 48 +/- 8%). The mechanoreflex was stimulated by stretching hindlimb muscle which likewise elicited significantly greater elevations in MAP and RSNA in SHR than WKY (Delta RSNA from baseline: 105 +/- 11 vs. 35 +/- 7%). Blockade of mechanoreceptors in muscle with gadolinium significantly attenuated the MAP and RSNA responses to contraction and stretch in SHR. These data suggest that 1) the exaggerated pressor response to activation of the EPR and muscle mechanoreflex in hypertension is mediated by abnormally large reflex-induced augmentations in SNA and 2) this accentuated sympathetic responsiveness is evoked, in part, by stimulation of muscle mechanoreceptors.