title: 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.
authors.affiliation: Hopital Marie Lannelongue, Université Paris Sud, Le Plessis Robinson, France.
authors.forename: J
authors.initials: J
authors.lastname: Le Pavec
authors.forename: F
authors.initials: F
authors.lastname: Perros
authors.forename: S
authors.initials: S
authors.lastname: Eddahibi
authors.forename: B
authors.initials: B
authors.lastname: Decante
authors.forename: P
authors.initials: P
authors.lastname: Dorfmuller
authors.forename: O
authors.initials: O
authors.lastname: Sitbon
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: M
authors.initials: M
authors.lastname: Mazmanian
authors.forename: P
authors.initials: P
authors.lastname: Herve