Korean J Pediatr.  2016 Jun;59(6):262-270. 10.3345/kjp.2016.59.6.262.

The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure

• Bae HK
• Lee H
• Kim KC
• Hong YM

• KMID: 2353156
• DOI: http://doi.org/10.3345/kjp.2016.59.6.262

Abstract

PURPOSE
Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF.
METHODS
The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed.
RESULTS
The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4.
CONCLUSION
Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function.

Keyword

Sildenafil citrate; Pulmonary hypertension; Gene expression

MeSH Terms

Animals
Arteries
Arterioles
B-Lymphocytes
Blotting, Western
Caspase 3
Collagen
Endothelins
Gene Expression
Heart
Hypertension
Hypertension, Pulmonary
Hypertrophy, Right Ventricular
Interleukin-6
Interleukins
Lung
Models, Animal*
Monocrotaline
Natriuretic Peptide, Brain
Necrosis
Nitric Oxide Synthase Type III
Rats*
Sildenafil Citrate*
Troponin I
Vascular Resistance
Ventricular Function, Right
Ventricular Pressure
Ventricular Remodeling*
Caspase 3
Collagen
Endothelins
Interleukin-6
Interleukins
Monocrotaline
Natriuretic Peptide, Brain
Nitric Oxide Synthase Type III
Sildenafil Citrate
Troponin I