The sympathetic nervous system and long-term blood pressure regulation

Abstract

There is considerable evidence that activation of the sympathetic nervous system plays an important role in the pathogenesis of several cardiovascular diseases, including hypertension. However, the mechanisms that account for sympathetic activation and the precise mechanisms that mediate neurally induced hypertension are unclear. In large part, this is due to the difficulty in assessing sympathetic function under chronic conditions. Consequently, acute observations are often extrapolated to infer that similar neural mechanisms are operative under more long-term conditions, an unwarrantable assumption. Nonetheless, considerable theoretical and experimental evidence points to the renal sympathetic nerves as the critical link between the sympathetic nervous system and long-term arterial pressure control. Both chronic increases and decreases in renal adrenergic activity alter renal excretory function and produce sustained elevations and reductions in arterial pressure, respectively. Recent observations, including those in dogs with hemibladders and one denervated kidney, indicate that chronic suppression of renal sympathetic nerve activity and attendant natriuresis are long-term compensatory responses to excess body fluid volumes and hypertension. Furthermore, studies combining deafferentation of cardiac receptors and sinoaortic baroreceptors with the split-bladder preparation suggest that chronic renal sympathoinhibition is mediated by baroreflex mechanisms, an especially important finding given the technical limitations in determining whether baroreflexes completely reset and impact sympathetic activity in chronic hypertension. In contrast to the chronic inhibitory effects of baroreflexes on sympathetic activity, other studies indicate that angiotensin II (Ang II) has sustained renal sympathoexcitatory effects. The opposing long-term effects of baroreflexes and Ang II on renal sympathetic nerve activity support two major hypotheses for sympathetic activation in hypertension: baroreflex dysfunction and activation of the renin-angiotensin system, abnormalities often associated with clinical hypertension.