The sympathetic nervous system in essential hypertension

Abstract

Enhanced activity of the sympathetic nervous system (SNS) could contribute to essential hypertension (EH). Results of over 80 studies measuring norepinephrine (NE) in EH patients show that only a minority of younger EH patients have elevated plasma NE. Younger EH patients also have increased renal NE spillover and elevated 24-hour NE levels. Another method to evaluate SNS in EH patients is examination of depressor responses to SNS blocking agents. The level of plasma NE predicts the degree of depressor response after acute clonidine administration in EH patients, suggesting increased SNS outflow in EH. Stimulation of SNS activity by stress, isometric exercise, or tilt table shows exaggerated NE responses in EH patients and young normotensive individuals from hypertensive-prone families. EH patients with high plasma NE tend to be younger, thinner, have higher pulse rates, greater cardiac indices, accentuated depressor responses to SNS inhibition, and blunted baroreflex sensitivity. Patients with EH also display enhanced vascular reactivity to infused NE despite high plasma NE, which should normally blunt vascular reactivity. Baroreceptors modulate blood pressure increases through central inhibition of SNS outflow. EH patients display diminished baroreceptor control early in the development of EH, as seen in younger patients with borderline or mild EH. However, most evidence indicates that baroreflex abnormalities in EH are a secondary event. Elevations of plasma epinephrine (E) are also seen in EH. Stress in EH subjects causes increases in plasma E, accompanied by sodium retention and enhanced vascular reactivity. Stress-induced increases in plasma E may result in prejunctional uptake of E in nerve terminals with release of E as a cotransmitter with NE--i.e., facilitation of NE release leading to postjunctional vasoconstriction and hypertension. Another catecholamine product of SNS activity, dopamine (DA), may contribute to EH by its effects on aldosterone and sodium excretion. DA inhibits aldosterone secretion and enhances sodium excretion. Studies in EH patients show reduced urinary-free DA responses to salt loading. This suggests an intrinsic deficiency of DA-modulated natriuretic mechanisms in EH.