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.
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Authors | J Le Pavec, F Perros, S Eddahibi, B Decante, P Dorfmuller, O Sitbon, D Lebrec, M Humbert, M Mazmanian, P Herve |
Journal | The European respiratory journal
(Eur Respir J)
Vol. 34
Issue 3
Pg. 731-9
(Sep 2009)
ISSN: 1399-3003 [Electronic] England |
PMID | 19324959
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Endothelins
- Enzyme Inhibitors
- Monocrotaline
- Nitric Oxide Synthase
- NG-Nitroarginine Methyl Ester
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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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