The sympathetic nervous system in hypertension: back to the future?

The seventeenth century London neuroanatomical school headed by Thomas Willis published the first images of the sympathetic nervous system. Nineteenth century European physiologists characterised these as the "pressor nerves". Von Euler's demonstration that the sympathetic transmitter was norepinephrine brought the field into the modern era. Sympathetic nervous system responses are regionally differentiated; human regional sympathetic activity is best studied by recording from postganglionic sympathetic efferents directed to the skeletal muscle vasculature (clinical microneurography) and by measurement of organ-specific norepinephrine release to plasma from sympathetic nerves (regional "norepinephrine spillover"). With these techniques, the sympathetic nervous system became accessible to clinical scientists, allowing the demonstration that sympathetic nervous system activation is crucial in the development and outcomes of cardiovascular disorders, most notably heart failure and essential hypertension. Activation of the renal sympathetic outflow is pivotal in the pathogenesis of essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. Although disputed, the case is strong that in hypertension, we are now on the cusp of effective "mechanisms to management" transition, with the use of catheter-based renal sympathetic nerve ablation for treating drug-resistant hypertension.