title: Bosentan does not improve pulmonary hypertension and lung remodeling in heart failure.
abstract: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction associated with heart failure (HF) carry a poor prognosis. Although endothelin receptor antagonists (ERAs) demonstrated benefits in pulmonary arterial hypertension, their efficacy in PH associated with HF was not specifically evaluated. 2 weeks after myocardial infarction (MI) rats received bosentan (100 or 200 mg·kg(-1)·day(-1)) or no treatment for 3 weeks. PH, RV hypertrophy and function as well as lung remodeling and function were evaluated. LV echocardiographic wall motion abnormality and function measured before treatment (2 weeks after MI) and after treatment (5 weeks after MI) were similar in MI control and MI treatment groups. HF induced PH and RV hypertrophy compared with sham: RV systolic pressure 39±5 versus 23±0.8 mmHg and RV/left ventricular+septum weight 52±7 versus 24±0.5% (all p<0.01). Bosentan did not significantly modify these parameters. In addition, bosentan did not improve depressed RV function measured by echocardiograph from the RV myocardial performance index and tricuspid annular plane systolic excursion. The respiratory pressure-volume relationship revealed that HF caused a restrictive lung syndrome with histological lung remodeling and fibrosis, also not improved by bosentan. Dual ERA therapy with bosentan does not reduce PH, RV hypertrophy and lung remodeling and dysfunction associated with ischaemic HF.
authors.affiliation: Research Center, Montreal Heart Institute and Dept of Medicine, Université de Montréal, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada.
authors.forename: B H
authors.initials: BH
authors.lastname: Jiang
authors.forename: J-C
authors.initials: JC
authors.lastname: Tardif
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: J
authors.initials: J
authors.lastname: Dupuis
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods; D065128:Endothelin Receptor Antagonists; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D009203:Myocardial Infarction / Q000473:pathology; D011379:Prognosis; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan