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Cirrhosis ameliorates monocrotaline-induced pulmonary hypertension in rats.

Abstract
Common bile duct ligation (CBDL) induces biliary cirrhosis and pulmonary vasodilatation. We tested whether CBDL ameliorates monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Five groups of rats were studied: controls; rats dosed with MCT (60 mg.kg(-1) subcutaneously); CBDL; rats dosed with MCT followed by CBDL on day 7; and rats dosed with MCT followed by CBDL (day 7) and L-NAME therapy between days 24 and 28. 28-day survival was 26% in the MCT group and 72% in the MCT+CBDL group. Pulmonary vascular resistance measured on days 21 and 28 increased in the MCT and MCT+CBDL+L-NAME groups, but returned to normal in the MCT+CBDL group on day 28. Pulmonary artery (PA) medial hypertrophy persisted in MCT+CBDL rats. PA inflammation increased in MCT+CBDL rats, with accumulation of both intra- and perivascular macrophages. Exhaled nitric oxide (NO) levels decreased in the MCT group and increased in the MCT+CBDL group, which showed upregulation of inducible NO synthase and normal endothelial NO synthase. Blood endothelin (ET)-1 increased in CBDL, MCT, and MCT+CBDL rats. Levels of ET(B) receptors increased and ET(A) receptors decreased in the MCT+CBDL group, whereas the opposite changes occurred in the MCT group. Biliary cirrhosis induces pulmonary vasodilation that ameliorates MCT-induced PH and improves survival. Upregulation of inducible NO synthase and ET(B) receptor and downregulation of ET(A) receptor may be involved.
AuthorsJ Le Pavec, F Perros, S Eddahibi, B Decante, P Dorfmuller, O Sitbon, D Lebrec, M Humbert, M Mazmanian, P Herve
JournalThe European respiratory journal (Eur Respir J) Vol. 34 Issue 3 Pg. 731-9 (Sep 2009) ISSN: 1399-3003 [Electronic] England
PMID19324959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Endothelins
  • Enzyme Inhibitors
  • Monocrotaline
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Common Bile Duct
  • Disease Models, Animal
  • Endothelins (metabolism)
  • Enzyme Inhibitors (therapeutic use)
  • Hypertension, Pulmonary (chemically induced, metabolism, prevention & control)
  • Ligation
  • Liver Cirrhosis, Biliary (etiology, metabolism, physiopathology)
  • Male
  • Monocrotaline
  • NG-Nitroarginine Methyl Ester (therapeutic use)
  • Nitric Oxide Synthase (metabolism)
  • Pulmonary Artery (pathology, physiopathology)
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation (physiology)

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