A Role for Brainstem Nitric Oxide in the Development of Muscle Mechanoreflex Overactivity in Hypertension

Abstract

In hypertensive individuals, exercise elicits excessive increases in arterial blood pressure (BP). These potentially dangerous elevations in BP increase the risk for adverse cardiac events or stroke during exercise. We have previously demonstrated that overactivity of the muscle mechanoreflex (MMR), a mechanically-sensitive reflex originating in skeletal muscle, contributes importantly to the generation of the exaggerated BP response to exercise in hypertension. Sensory information elicited by activation of the MMR is processed within nucleus tractus solitarius (NTS) of the medulla oblongata. Evidence suggests that, under healthy conditions, the endogenous production of nitric oxide (NO) within the NTS attenuates the BP response mediated by the MMR. Therefore, we hypothesized that the exaggerated increase in BP evoked by the MMR in hypertension is due to a decrease in the production of NO within the NTS. PURPOSE: To determine the role of endogenously produced NO within the NTS in the development of MMR overactivity in hypertension. METHODS: The MMR was selectively activated by passively stretching hindlimb skeletal muscle before and after the microdialysis of the non-specific NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 5.0 mM) in the NTS of male normotensive Wistar Kyoto (WKY; n=5) and spontaneously hypertensive (SHR; n=5) rats. By using L-NAME, the endogenous production of NO was experimentally reduced. RESULTS: Prior to the dialysis of L-NAME, preferential activation of the MMR by stretch resulted in significantly larger increases in mean BP in SHR (34±6 mmHg) than WKY (20±4 mmHg). In both groups, dialysis of L-NAME augmented the BP response to stretch. Interestingly, the percent by which BP was increased after L-NAME in response to stretch was markedly larger in WKY (50±15%) than SHR (26±4%). CONCLUSION: Collectively, the data suggest i) decreasing the endogenous production of NO within the NTS of normotensive rats partially recapitulates the MMR overactivity manifest in hypertension and ii) although it may be reduced, NO production is not completely absent within the NTS of hypertensive rats. These findings are consistent with the concept that reductions in the endogenous production of NO within the NTS contribute to MMR overactivity in hypertension. Supported by AHA SDG 0735355N