title: N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats.
abstract: BACKGROUND
  The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.
  
  
  METHODS
  Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14-28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.
  
  
  RESULTS
  The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).
  
  
  CONCLUSIONS
  Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Chaumais
authors.forename: Benoît
authors.initials: B
authors.lastname: Ranchoux
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.forename: Ly
authors.initials: L
authors.lastname: Tu
authors.forename: Florence
authors.initials: F
authors.lastname: Lecerf
authors.forename: Nicolas
authors.initials: N
authors.lastname: Raymond
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.forename: Laura
authors.initials: L
authors.lastname: Price
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cohen-Kaminsky
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: UMRS 999, INSERM et Univ, Paris-Sud, Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France. frederic.perros@inserm.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D016686:Monocrotaline; D000111:Acetylcysteine