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Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505
To
determine whether the chronically denervated kidney is supersensitive
to either physiological or pathophysiological plasma levels of
norepinephrine (NE), studies were conducted in conscious dogs subjected
to unilateral renal denervation and surgical division of the urinary
bladder into hemibladders to allow separate 24-h urine collection from
denervated 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 · min1.
Twenty-four-hour control values for mean arterial pressure (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 ~3,000 pg/ml or plasma concentrations of NE at least threefold
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 rates of
sodium and potassium from denervated and innervated kidneys. In marked
contrast, pharmacological plasma levels of NE (~7,000 pg/ml) produced
chronic increases in MAP (to 116 ± 2% of control) and sustained
reductions in Den/Inn for urinary sodium and potassium excretion to 57 ± 4 and 68 ± 5% of control, respectively, indicating a lower
excretion rate of these electrolytes from denervated vs. innervated
kidneys. We conclude that the chronically denervated kidney does not
exhibit an exaggerated antinatriuretic response to either physiological
or pathophysiological levels of circulating NE. It is therefore
unlikely that renal denervation supersensitivity is a confounding issue
in studies employing chronic renal denervation to elucidate the role of
the renal nerves in the regulation of sodium excretion.
renal nerves; norepinephrine; sodium excretion
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