title: Aliskiren reduces portal pressure and intrahepatic resistance in biliary cirrhotic rats.
abstract: BACKGROUND
  It is a well-accepted fact that angiotensin II (Ang II) contributes to increased vascular tone in cirrhotic livers. However, aliskiren attenuates the effect of Ang II through direct renin inhibition. Our study aimed to evaluate the effects of aliskiren on portal pressure and intrahepatic resistance in bile duct ligated (BDL) rats.
  
  
  METHODS
  The effects of acute intravenous infusion (1 mg or 3 mg) or a course of 2-day oral administration of aliskiren (20 mg/kg/day) on blood pressure and portal pressure were evaluated in BDL and sham rats. Intrahepatic resistance was evaluated by a liver perfusion study isolated in situ. Ang II efflux was measured by Enzyme-linked immunosorbent assay (ELISA). The hepatic gene expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT(1)R) was analyzed with quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Aliskiren infusion intravenously reduced portal pressure with a minimal effect on blood pressure in BDL rats. Direct infusion of aliskiren in an isolated cirrhotic liver caused greater vasorelaxation and decreased hepatic production of Ang II. Two days of aliskiren treatment reduced portal pressure and hepatic ACE mRNA; in addition, it improved the vasodilator response to acetylcholine in the cirrhotic livers and decreased Ang II efflux.
  
  
  CONCLUSIONS
  Aliskiren reduced portal pressure in cirrhotic rats. The portal hypotensive effect of aliskiren was related to the amelioration of the Ang II induced intrahepatic vasoconstriction.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Che-Chang
authors.initials: CC
authors.lastname: Chan
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Lee
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology; D008297:Male; D017082:Portal Pressure / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D000577:Amides; D005650:Fumarates; C446481:aliskiren