PT  - JOURNAL ARTICLE
AU  - L.C. Price
AU  - D. Montani
AU  - C. Tcherakian
AU  - P. Dorfmüller
AU  - R. Souza
AU  - N. Gambaryan
AU  - M-C. Chaumais
AU  - D.M. Shao
AU  - G. Simonneau
AU  - L.S. Howard
AU  - I.M. Adcock
AU  - S.J. Wort
AU  - M. Humbert
AU  - F. Perros
TI  - Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats
AID  - 10.1183/09031936.00028310
DP  - 2011 Apr 01
TA  - European Respiratory Journal
PG  - 813--822
VI  - 37
IP  - 4
4099  - http://erj.ersjournals.com/content/37/4/813.short
4100  - http://erj.ersjournals.com/content/37/4/813.full
SO  - Eur Respir J2011 Apr 01; 37
AB  - Pulmonary arterial hypertension (PAH) is associated with dysregulated bone morphogenetic protein receptor (BMPR)-II signaling and pulmonary vascular inflammation. We evaluated the effects of dexamethasone on monocrotaline (MCT)-induced PAH in rats for potential reversal of PAH at late time-points.Saline-treated control, MCT-exposed, MCT-exposed and dexamethasone-treated rats (5 mg·kg−1·day−1, 1.25 mg·kg−1 and 2.5 mg·kg−1·48 h−1) were evaluated at day 28 and day 35 following MCT for haemodynamic parameters, right ventricular hypertrophy, morphometry, immunohistochemistry, and IL6 and BMPR2 expression.Dexamethasone improved haemodynamics and pulmonary vascular remodelling, preventing PAH development at early (day 1–14 and 1–28) and reversing PAH at late (day 14–28 and 21–35) time-points following MCT, as well as improving survival in MCT-exposed rats compared with controls. Both MCT-induced pulmonary IL6 overexpression and interleukin (IL)-6-expressing adventitial inflammatory cell infiltration were reduced with dexamethasone. This was associated with pulmonary BMPR2 downregulation following MCT, which was increased with dexamethasone, in whole lung and control pulmonary artery smooth muscle cells. Dexamethasone also reduced proliferation of rat pulmonary artery smooth muscle cells in vitro.Experimental PAH can be prevented and reversed by dexamethasone, and survival is improved. In this model, mechanisms may involve reduction of IL-6-expressing inflammatory cells, restoration of pulmonary BMPR2 expression and reduced proliferation of vascular smooth muscle cells.