Involvement of nitric oxide in the suppressive effect of 17beta-estradiol on endothelin-1 overproduction in ischemic acute renal failure.
It is known that 17beta-estradiol (E2-beta) increases the production of nitric oxide. We have demonstrated that E2-beta prevents renal injury and suppresses renal endothelin-1 overproduction in ischemic acute renal failure in rats. In the present study, we investigated whether N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, can reverse the effect of E2-beta in ischemic acute renal failure. Ischemic acute renal failure was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, 2 weeks after contralateral nephrectomy. Pre-ischemic treatment with E2-beta (100 microg/kg, intravenously) attenuated the ischemia/ reperfusion-induced renal dysfunction and suppressed the increment of renal endothelin-1 content 24 hours after reperfusion. The effects of E2-beta on renal dysfunction and increased endothelin-1 content in acute renal failure rats were reversed by pretreatment with N(G)-nitro-L-arginine methyl ester (0.3 mg/kg, intravenously). An in vivo microdialysis study revealed that the concentration of nitric oxide metabolites in the kidney was reduced during ischemia, and quickly recovered after reperfusion in E2-beta-treated acute renal failure rats, compared with cases in untreated acute renal failure rats. This recovery of renal nitric oxide metabolite concentration with E2-beta was abolished by the pretreatment with N(G)-nitro-Larginine methyl ester. These findings suggest that nitric oxide is closely related to suppressive effect of E2-beta on renal endothelin-1 overproduction in acute renal failure rats and this suppression is probably involved in the beneficial effect of E2-beta on ischemia/reperfusion-induced renal injury.
Shibata
Yujiro
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Takaoka
Masanori
M
Maekawa
Daisuke
D
Kuwahara
Chika
C
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester