title: Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension.
abstract: BACKGROUND
  Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH.
  
  
  OBJECTIVE
  The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats.
  
  
  METHODS
  Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 microg . kg(-1) . day(-1), or underwent sham nebulization with saline.
  
  
  RESULTS
  After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed.
  
  
  CONCLUSIONS
  We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.
authors.affiliation: Department of Internal Medicine, Justus Liebig Universität Giessen, Germany. ralph.schermuly@innere.med.uni-giessen.de
authors.forename: Ralph Theo
authors.initials: RT
authors.lastname: Schermuly
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Yilmaz
authors.forename: Hossein Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Kathrin
authors.initials: K
authors.lastname: Woyda
authors.forename: Soni
authors.initials: S
authors.lastname: Pullamsetti
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulz
authors.forename: Tobias
authors.initials: T
authors.lastname: Gessler
authors.forename: Rio
authors.initials: R
authors.lastname: Dumitrascu
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology*; D016686:Monocrotaline / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D014665:Vasodilator Agents; D016686:Monocrotaline; D016285:Iloprost