RT Journal Article
SR Electronic
T1 Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 813
OP 822
DO 10.1183/09031936.00028310
VO 37
IS 4
A1 L.C. Price
A1 D. Montani
A1 C. Tcherakian
A1 P. Dorfmüller
A1 R. Souza
A1 N. Gambaryan
A1 M-C. Chaumais
A1 D.M. Shao
A1 G. Simonneau
A1 L.S. Howard
A1 I.M. Adcock
A1 S.J. Wort
A1 M. Humbert
A1 F. Perros
YR 2011
UL http://erj.ersjournals.com/content/37/4/813.abstract
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.