Abnormal norepinephrine release in uremia

Sympathetic nervous activity, which we defined as the relative rate of appearance of norepinephrine (NE) in plasma, was investigated in normal men (control) and uremic patients with two-step steady-state cold NE infusions. Both basal venous NE and the NE metabolic clearance rate (C(NE), calculated from the infusion rate and the steady-state increment in venous NE) were higher in patients than in controls. The calculated appearance rate of NE in venous plasma (C(NE) x basal NE) was much higher in the patients, suggesting increased NE release and therefore sympathetic nervous hyperactivity in these patients. Of interest was the fall in both C(NE) and NE appearance rate at the higher infusion rate in controls, but not patients. These data suggest that circulating NE may normally suppress sympathetic nervous activity, but that this negative feedback mechanism is impaired in uremia.