Involvement of nitric oxide in the suppressive effect of 17beta-estradiol on endothelin-1 overproduction in ischemic acute renal failure.

It is known that 17β-estradiol (E 2 -β) increases the production of nitric oxide. We have demonstrated that E 2 -β 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 E 2 -β 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 E 2 -β (100 μg/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 E 2 -β 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 E 2 -β-treated acute renal failure rats, compared with cases in untreated acute renal failure rats. This recovery of renal nitric oxide metabolite concentration with E 2 -β was abolished by the pretreatment with N G -nitro-L-arginine methyl ester. These findings suggest that nitric oxide is closely related to suppressive effect of E 2 -β on renal endothelin-1 overproduction in acute renal failure rats and this suppression is probably involved in the beneficial effect of E 2 -β on ischemia/reperfusion-induced renal injury.