Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice.
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 x ml(-1) x h(-1), 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 microg/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 microl/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.
Wang
Wei
W
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Falk
Sandor A
SA
Jittikanont
Suparoek
S
Gengaro
Patricia E
PE
Edelstein
Charles L
CL
Schrier
Robert W
RW
D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D019446:Endotoxemia / Q000150:complications*; D004837:Epinephrine / Q000097:blood; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000294:innervation*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine