Improvement of Portal Hypertension and Hepatic Blood Flow in Liver Cirrhosis by Estrogen

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Background : In this study, we investigated the effects of estrogen on nitric oxide synthase activity and nitric oxide production using the cirrhotic rat liver.Material and Methods : Cirrhosis was induced by dimethylnitrosamine. Estradiol valerate was subcutaneously injected 2 times at week 4 after dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an estrogen receptor antagonist, ICI-182.780, was performed 2 days before administration of estradiol valerate. Portal pressure and hepatic blood flow were measured. Nitric oxide synthase activity was assessed by L-citrulline generation. Sinusoidal endothelial cells were isolated from the cirrhotic rat liver and cultured. The cells were incubated with estradiol and/or ICI-182.780 for 24 hours. Images for nitric oxide in sinusoidal endothelial cells were obtained using diaminofluorescein-2 diacetate.Results : Cirrhotic rats treated with estradiol valerate showed a significant decrease in portal pressure and a significant increase in hepatic blood flow compared to those of control cirrhosis rats. However, in cirrhotic rats treated with ICI-182.780, the reduction of portal pressure and elevation of hepatic blood flow were completely inhibited. In cirrhotic rats treated with estradiol valerate, nitric oxide synthase activity was increased compared to that in control cirrhotic rats. The fluorescent level of intracellular nitric oxide in estradiol-stimulated cultured sinusoidal endothelial cells was higher than that in non-treated sinusoidal endothelial cells.Conclusions : The present study indicated that estrogen plays an important role in the enhancement of nitric oxide production in sinusoidal endothelial cells of cirrhotic liver and reduces the portal pressure in cirrhotic rats.