title: The ability of 17 β-estradiol to attenuate intrahepatic vasoconstriction to endothelin-1 in female rats is lost in cirrhosis.
abstract: OBJECTIVE
  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: Division of Gastroenterology, Department of Medicine.
authors: Hsin-Ling
authors: HL
authors: Ho
authors: Division of Gastroenterology, Department of Medicine; Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Fa-Yauh
authors: FY
authors: Lee
authors: Division of Gastroenterology, Department of Medicine; Department and Institute of Pharmacology; Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan; National Yang-Ming University Hospital, Yilan, Taiwan.
authors: Shao-Jung
authors: SJ
authors: Hsu
authors: Department of Medical Affair and Planning, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Sun-Sang
authors: SS
authors: Wang
authors: Endoscopy Center for Diagnosis and Treatment; Department and Institute of Pharmacology; Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: I-Fang
authors: IF
authors: Hsin
authors: Division of Gastroenterology, Department of Medicine; Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Hui-Chun
authors: HC
authors: Huang
authors: Division of Gastroenterology, Department of Medicine; Department and Institute of Pharmacology.
authors: Jing-Yi
authors: JY
authors: Lee
authors: Division of Gastroenterology, Department of Medicine; aculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Han-Chieh
authors: HC
authors: Lin
authors: Faculty of Medicine. National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors: Shou-Dong
authors: SD
authors: Lee
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006499:Hepatic Artery / Q000187:drug effects / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol; D012313:RNA