ROLE OF SYMPATHETIC EFFERENT NERVES IN BLOOD-PRESSURE REGULATION AND IN HYPERTENSION

This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed. The pathophysiological basis of altered cardiovascular control in these various disorders along with the effects of drugs with known mechanisms have advanced our understanding of the role in humans of sympathetic efferent nerves in blood pressure regulation and in hypertension.