The ability of 17 β-estradiol to attenuate intrahepatic vasoconstriction to endothelin-1 in female rats is lost in cirrhosis

Abstract

Background and rationale. The control of Endothelin-1 (ET-1)-mediated intrahepatic vasoconstriction in cirrhosis is beneficial for the alleviation of relevant complications. Cirrhosis is accompanied by hypogonadism and altered sex hormone status. Besides- sex hormones have vasoactive effects- but it is unknown if they influence vascular function in cirrhosis. This study aimed to investigate the roles of sex hormones in hepatic vascular reactions to ET-1 in cirrhosis. Liver cirrhosis was induced in Spraque-Dawley male and female rats with common bile duct ligation (BDL). Sham-operated (Sham) rats were controls. On the 43rd day after operations- intrahepatic vascular concentration-response curves to ET-1 were obtained with the following preincubatioins: 1) vehicle; 2) 17β-estradiol; 3) progesterone; 4) testosterone. Livers from sham and BDL rats were dissected for real-time polymerase chain reaction analysis of estrogen- progesterone and testosterone receptors.Results. Compared with sham males perfused with vehicle- sham females presented higher perfusion pressure changes to ET-1 which was reversed only by 17β-estradiol. In cirrhosis- compared with males- 17β-estradiol no longer attenuated vascular responsiveness to ET-1 in females. In females- BDL rats had lower hepatic estrogen receptor α(ERα) mRNA expression than that in sham rats.Conclusions. The sham females showed a stronger intrahepatic vascular constrictive effect to ET-1 than sham males- which could be reversed by 17β-estradiol. However- the influence of 17β-estradiol was lost in cirrhotic females- which may be attributed- at least partly- to intrahepatic ERa down-regulation in females with cirrhosis.