RENAL DENERVATION SUPERSENSITIVITY REVISITED

To determine whether the chronically denervated kidney is supersensiti ve to either physiological or pathophysiological plasma levels of nore pinephrine (NE), studies were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bla dder into hemibladders to allow separate 24-h urine collection from de nervated and innervated kidneys. Plasma NE concentration was increased by chronic infusion of NE (4-5 days) at rates of 25, 100, and 200 ng. kg(-1).min(-1). Twenty-four-hour control values for mean arterial pres sure (MAP), plasma NE concentration, and ratios for urinary sodium and potassium excretion from denervated and innervated kidneys (Den/Inn) were 94 +/- 4 mmHg, 145 +/- 24 pg/ml, 1.05 +/- 0.05, and 0.97 +/- 0.07 , respectively. With infusions of NE producing plasma levels of NE of up to similar to 3,000 pg/ml or plasma concentrations of NE at least t hreefold greater than present under most pathophysiological conditions and during acute activation of the sympathetic nervous system, there were no significant long-term changes in MAP or relative excretion rat es of sodium and potassium from denervated and innervated kidneys. In marked contrast, pharmacological plasma levels of NE (similar to 7,000 pg/ml) produced chronic increases in MAP (to 116 +/- 2% of control) a nd sustained reductions in Den/Inn for urinary sodium and potassium ex cretion to 57 +/- 4 and 68 +/- 5% of control, respectively, indicating a lower excretion rate of these electrolytes from denervated vs. inne rvated kidneys. We conclude that the chronically denervated kidney doe s not exhibit an exaggerated antinatriuretic response to either physio logical or pathophysiological levels of circulating NE. It is therefor e unlikely that renal denervation supersensitivity is a confounding is sue in studies employing chronic renal denervation to elucidate the ro le of the renal nerves in the regulation of sodium excretion.