Tempol protects against ischemic acute renal failure by inhibiting renal noradrenaline overflow and endothelin-1 overproduction.
The effects of tempol, a superoxide dismutase mimetic, on ischemia/reperfusion-induced acute renal failure (ARF), noradrenaline (NA) overflow and endothelin-1 (ET-1) overproduction in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine concentration, and fractional excretion of sodium, NA concentrations in renal venous plasma, and renal ET-1 contents were determined. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Pre-ischemic treatment with tempol (10, 100 mg/kg, i.v.) dose-dependently attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, which were also significantly suppressed by the tempol treatment. There was a significant increase in NA concentrations in renal venous plasma after the ischemia/reperfusion, and this increase was markedly suppressed by the treatment with tempol. In addition, tempol treatment significantly attenuated the increment of ET-1 content in the kidney exposed to the ischemia/reperfusion. These findings suggest that tempol improves the post-ischemic renal injury by inhibiting the neural activity of renal sympathetic nerve and ET-1 overproduction.
Fujii
Toshihide
T
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Takaoka
Masanori
M
Ohkita
Mamoru
M
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000188:drug therapy*; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D019332:Endothelin-1 / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D019332:Endothelin-1; D013113:Spin Labels; C001803:tempol; D009638:Norepinephrine