Improvement of portal hypertension and hepatic blood flow in cirrhotic rats by oestrogen.
BACKGROUND
In this study, we investigated the effects of oestrogen on nitric oxide synthase activity and nitric oxide production using the cirrhotic rat liver.


METHODS
Cirrhosis was induced by dimethylnitrosamine. Estradiol valerate was subcutaneously injected twice at week 4 after dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an oestrogen 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 h. 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 with 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 with that in control cirrhotic rats. The fluorescent level of intracellular nitric oxide in estradiol-stimulated, cultured, sinusoidal endothelial cells was higher than that in nontreated sinusoidal endothelial cells.


CONCLUSIONS
The present study indicated that oestrogen 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.
Sakamoto
M
M
Second Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Ueno
T
T
Nakamura
T
T
Sakata
R
R
Hasimoto
O
O
Torimura
T
T
Sata
M
M
D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008099:Liver / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004965:Estrogen Antagonists; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat