Left ventricular hypertrophy in rats with biliary cirrhosis

Hepatology. 2003 Sep;38(3):589-98. doi: 10.1053/jhep.2003.50369.


Portal hypertension induces neuroendocrine activation and a hyperkinetic circulation state. This study investigated the consequences of portal hypertension on heart structure and function. Intrahepatic portal hypertension was induced in male Sprague-Dawley rats by chronic bile duct ligation (CBDL). Six weeks later, CBDL rats showed higher plasma angiotensin-II and endothelin-1 (P <.01), 56% reduction in peripheral resistance and 73% reduction in pulmonary resistance (P <.01), 87% increase in cardiac index and 30% increase in heart weight (P <.01), and increased myocardial nitric oxide (NO) synthesis. In CBDL rats, macroscopic analysis demonstrated a 30% (P <.01) increase in cross-sectional area of the left ventricular (LV) wall without changes in the LV cavity or in the right ventricle (RV). Histomorphometric analysis revealed increased cell width (12%, P <.01) of cardiomyocytes from the LV of CBDL rats, but no differences in myocardial collagen content. Myocytes isolated from the LV were wider (12%) and longer (8%) than right ventricular myocytes (P <.01) in CBDL rats but not in controls. CBDL rats showed an increased expression of ANF and CK-B genes (P <.01). Isolated perfused CBDL hearts showed pressure/end-diastolic pressure curves and response to isoproterenol identical to sham hearts, although generated wall tension was reduced because of the increased wall thickness. Coronary resistance was markedly reduced. This reduction was abolished by inhibition of NO synthesis with N-nitro-L-arginine. Expression of eNOS was increased in CBDL hearts. In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment. This observation could be relevant to patients with cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Ducts
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Heart / drug effects
  • Heart / physiopathology
  • Hypertension, Portal / complications*
  • Hypertension, Portal / etiology
  • Hypertension, Portal / pathology
  • Hypertension, Portal / physiopathology
  • Hypertrophy, Left Ventricular / etiology*
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Ligation
  • Liver Cirrhosis, Biliary / complications
  • Liver Cirrhosis, Biliary / etiology*
  • Liver Cirrhosis, Biliary / pathology
  • Liver Cirrhosis, Biliary / physiopathology
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nitric Oxide Synthase / metabolism
  • Nitroarginine / pharmacology
  • Organ Size
  • Rats
  • Rats, Sprague-Dawley


  • Enzyme Inhibitors
  • Isoenzymes
  • Nitroarginine
  • Nitric Oxide Synthase
  • Cyclic GMP