Abstract
In hypertension, the blood pressure (BP) response to exercise is abnormally elevated. We have previously demonstrated that overactivity of the skeletal muscle mechanoreflex (MMR) plays a significant role in generating this exaggerated BP response to exercise. Yet the mechanisms underlying MMR overactivity remain unknown. Sensory information elicited by activation of the MMR is processed within the nucleus tractus solitarius (NTS) of the medulla oblongata. In normotensive rats, nitric oxide (NO) within the NTS is known to buffer MMR function. Recent evidence suggests the production of reactive oxygen species in the NTS, specifically superoxide (a NO scavenger), is increased in hypertension. Therefore, augmentations in superoxide production could reduce the NO available for biological activity. This may reduce the buffering capacity of NO in hypertension resulting in MMR overactivity. PURPOSE: To determine the effects of endogenously produced superoxide on MMR activity in male normotensive Wistar-Kyoto (WKY; n=4) and Spontaneously Hypertensive (SHR; n=5) rats. METHODS: The MMR was selectively activated by passively stretching hindlimb skeletal muscle before and after the microdialysis of the superoxide dismutase mimetic, tempol (30 μM) in the NTS. Superoxide dismutase is the endogenous enzyme responsible for the breakdown of superoxide. RESULTS: Activation of the MMR by stretch resulted in significantly larger increases in mean BP in SHR (58±5 mmHg) than WKY (22±3 mmHg). In both groups, dialysis of tempol reduced the BP response to stretch. Interestingly, the magnitude of the tempol-induced decrease in BP in response to MMR activation was larger in SHR (-24±6 mmHg) compared to WKY (-7±4 mmHg). Despite this larger effect, the stretch-induced augmentation in BP in SHR treated with tempol was greater than the BP increase elicited by stretch in untreated WKY. CONCLUSIONS: The results demonstrate that endogenously produced superoxide modulates MMR activity in both WKY and SHR animals. Further, the findings suggest that decreasing superoxide within the NTS can partially correct the exaggerated BP response to activation of the MMR in SHR. As such, the data are consistent with the concept that increases in superoxide production within the NTS contribute to MMR dysfunction in hypertension. Supported by HL-088422
Published Version
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