Involvement of Nitric Oxide in the Suppressive Effect of 17??-Estradiol on Endothelin-1 Overproduction in Ischemic Acute Renal Failure

Abstract

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.