Increased Plasma Norepinephrine and Sympathetic Nervous Activity in Essential Hypertensive and Uremic Humans

Summary: We investigated the relationship between hypertension and increased sympathoadrenal activity in previously normotensive, stable maintenance hemodialysis patients (uremics) who developed hypertension subsequent to the onset of chronic renal failure. In age-matched groups, supine morning plasma norepinephrine (NE) concentrations (pg/ml) were elevated in uremics (401 ± 26, p < 0.00001, n = 23) and essential hypertensives (340 ± 23, p < 0.01, n = 29) compared to normal controls (260 ± 18, n = 24). To further investigate the functional significance of increased sympathoadrenal activity in uremia, a subset of dialysis patients was studied during chronic clonidine therapy. Compared to placebo baseline, clonidine (mean dose 0.4 mg/day) caused parallel decreases in mean arterial pressure (MAP) (−8 ± 2 mm Hg, p < 0.05), heart rate (HR) (− 13 ± 3 b/min, p < 0.05), plasma NE (−84 ± 13 pg/ml, p < 0.01), and plasma epinephrine (−24 ± 4 pg/ml, p < 0.01). Clonidine exerted balanced effects on cardiac output and systemic vascular resistance while blood volume and plasma renin activity were slightly increased. We conclude that the increased sympathoadrenal activity in uremia contributes to chronically increased arterial pressure in a pattern similar to essential hypertension. Central sympatholytic drugs are effective antihypertensive agents in uremia.