Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-1 overproduction.
We investigated whether the treatment with 17 beta-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17 beta-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24 h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17 beta-oestradiol (20 or 100 microg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17 beta-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17 beta-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. takaoka@oups.ac.jp
Masanori
M
Takaoka
Mikihiro
M
Yuba
Toshihide
T
Fujii
Mamoru
M
Ohkita
Yasuo
Y
Matsumura
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D004958:Estradiol / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D004958:Estradiol