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) 17ß-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 17 ß-estradiol. In cirrhosis, compared with males, 17 ß-estradiol no longer attenuated vascular responsiveness to ET-1 in females. In females, BDL rats had lower hepatic estrogen receptor α(ERβα) 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 17 β-estradiol was lost in cirrhotic females, which may be attributed, at least partly, to intrahepatic ER α down-regulation in females with cirrhosis.

• Authors: Hsin-Ling Ho, Fa-Yauh Lee, Shao-Jung Hsu, Sun-Sang Wang, I-Fang Hsin, Hui-Chun Huang, Jing-Yi Lee, Han-Chieh Lin, Shou-Dong Lee
• Journal: Annals of hepatology (Ann Hepatol) 2015 May-Jun Vol. 14 Issue 3 Pg. 404-13 ISSN: 1665-2681 [Print] Mexico
• PMID: 25864222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Estrogen Receptor alpha
• Estrogens
• Estradiol
• RNA

Topics

• Animals
• Endothelin-1 (pharmacology)
• Estradiol (pharmacology)
• Estrogen Receptor alpha (biosynthesis, genetics)
• Estrogens (pharmacology)
• Female
• Gene Expression Regulation
• Hepatic Artery (drug effects, physiopathology)
• Liver (blood supply, metabolism)
• Liver Cirrhosis, Experimental (drug therapy, genetics, physiopathology)
• Male
• RNA (genetics)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Vasoconstriction (drug effects)