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Involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline-induced endothelial apoptosis in rats.
- Source :
-
Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2011 May; Vol. 89 (5), pp. 345-54. Date of Electronic Publication: 2011 May 27. - Publication Year :
- 2011
-
Abstract
- Mutations in bone morphogenetic protein (BMP) receptor II (BMPR2) are associated with the apoptosis of the pulmonary artery endothelial cells and the loss of the pulmonary small vessels. The present study was designed to investigate the involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline (MCT)-induced endothelial apoptosis in rats. Models of pulmonary arterial hypertension in rats were established by a single intraperitoneal injection of MCT (60 mg/kg). Fluoxetine (2 and 10 mg/kg) was intragastrically administered once a day. After 21 days, MCT caused pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling and significantly reduced the BMPR2 expression in lungs and pulmonary arteries. Fluoxetine dose-dependently inhibited MCT-induced pulmonary arterial hypertension and effectively protected the lungs against MCT-induced endothelial apoptosis, reduction in the number of alveolar sacs, and loss of the pulmonary small vessels. Fluoxetine reversed the expression of cyclic guanosine 3',5'-monophosphate-dependent kinase І, BMPR2, phospho-Smad1, β-catenin, and reduced the expression of caspase 3 in rat lungs. These findings suggest that BMPR2 is probably involved in the protective effect of fluoxetine against MCT-induced endothelial apoptosis in rats.
- Subjects :
- Animals
Blood Pressure drug effects
Bone Morphogenetic Protein Receptors, Type II genetics
Caspase 3 metabolism
Cyclic GMP-Dependent Protein Kinases metabolism
Endothelial Cells cytology
Fluoxetine therapeutic use
Gene Expression drug effects
Gene Expression genetics
Hypertension, Pulmonary metabolism
Hypertension, Pulmonary pathology
Hypertension, Pulmonary prevention & control
Hypertrophy, Right Ventricular pathology
Hypertrophy, Right Ventricular prevention & control
Lung blood supply
Lung drug effects
Lung metabolism
Lung pathology
Male
Microvessels drug effects
Microvessels pathology
Phosphorylation drug effects
Pulmonary Artery drug effects
Pulmonary Artery metabolism
Pulmonary Artery pathology
Rats
Rats, Wistar
Smad1 Protein metabolism
beta Catenin metabolism
Apoptosis drug effects
Bone Morphogenetic Protein Receptors, Type II metabolism
Endothelial Cells drug effects
Fluoxetine pharmacology
Hypertension, Pulmonary chemically induced
Monocrotaline pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1205-7541
- Volume :
- 89
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Canadian journal of physiology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21619414
- Full Text :
- https://doi.org/10.1139/y11-024