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Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
Acute renal
failure (ARF) contributes substantially to the high morbidity and
mortality observed during endotoxemia. We hypothesized that selective
blockade of the renal nerves would be protective against ARF during the
early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip
in mice]. At 16 h after LPS, there was no change in mean arterial
pressure, but plasma epinephrine (4,604 ± 719 vs. 490 ± 152 pg/ml, P < 0.001), norepinephrine (2,176 ± 306 vs. 1,224 ± 218 pg/ml, P < 0.05), and plasma renin
activity (40 ± 5 vs. 27 ± 2 ng · ml
1 · h1,
P < 0.05) were higher in the LPS-treated vs. control
mice. The high plasma renin activity level decreased to the control
level with renal denervation in endotoxemic mice. After intravenous injection of phentolamine (200 µg/kg), the decrement in mean arterial pressure was significantly greater in LPS-treated vs. control mice
(19.4 ± 3.5 vs. 8.1 ± 1.5 mmHg, P < 0.01).
Sixteen hours after LPS administration, there were significant
decreases in glomerular filtration rate (52 ± 18 vs. 212 ± 23 µl/min, P < 0.01) and renal blood flow (0.58 ± 0.08 vs. 0.85 ± 0.06 ml/min, P < 0.01) in
sham-operated mice. The decrement in glomerular filtration rate during
endotoxemia was significantly attenuated in mice with denervated
kidneys (32 vs. 79%). Moreover, there was no change in renal blood
flow during endotoxemia in mice with renal denervation. The present
results therefore demonstrate a protective role of renal denervation
during normotensive endotoxemia-related ARF in mice, an effect that may
be, at least in part, due to a diminished activation of the
renin-angiotensin system.
glomerular filtration rate; renal blood flow; epinephrine; norepinephrine; sepsis
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