The sympathetic nervous system plays an important role in the pathogenesis of hypertension, although the precise mechanisms are unclear. This is because techniques are needed to critically evaluate the role of the nervous system in the chronic regulation of arterial pressure. There has been considerable interest in the impact of baroreflexes on sympathetic activity and arterial pressure in chronic hypertension, particularly since baroreflex dysfunction is commonly associated with hypertension. As baroreflexes reset in the direction of the prevailing level of pressure, it has been argued that they cannot possibly play a role in long-term regulation of arterial pressure. However, novel approaches in chronically instrumented animals have recently shown that baroreflexes do not totally reset in hypertension and that they promote sodium excretion by producing sustained reductions in renal sympathetic nerve activity (RSNA). These findings suggest that baroreflex mediated inhibition of RSNA may play an important compensatory role in hypertensxon. The proposed studies will evaluate this concept by employing 2 techniques: 1) prolonged activation of the baroreflex by bilateral electrical stimulation of the carotid sinus, and 2) abrogation of the baroreflex by sinoaortic denervation (SAD). As carotid baroreceptor afferent input into the CNS will be constant during carotid sinus stimulation, this will permit several novel determinations including: 1) the long-term hypotensive response to prolonged baroreflex activation in normal dogs and the role of the renal nerves in mediating the hypotension, and 2) the long-term hypotensive response to baroreflex activation in hypertensive dogs and the importance of a responsive renin-angiotensin system in mediating the hypotension. The compensatory role of the baroreflex in attenuating different models of hypertension will be tested further by SAD. We hypothesize that sustained baroreflex activation can attenuate the severity of hypertension by chronically suppressing RSNA. Further, we propose that suppression of renin secretion contributes to the hypotensive effects of baroreflex mediated renal sympathoinhibition. Thus, we expect the hypotensive response to baroreflex activation to be attenuated in hypertension produced by infusion of either angiotensin or aldosterone, but not in obesity hypertension in which increased renin secretion is linked to increased RSNA. Insight from these studies will be directly relevant to neurally mediated renal compensations in hypertension.
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