Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, cilostazol therapy, monocrotaline, pulmonary arterial hypertension, CONTINUOUS INTRAVENOUS EPOPROSTENOL, SMOOTH-MUSCLE CELLS, PROLIFERATION, BOSENTAN, DISEASE, Animals, Blood Pressure, Body Weight, Cilostazol, Connexin 43, Disease Models, Animal, Endothelium, Vascular, Gene Expression, Hypertension, Pulmonary, Male, Monocrotaline, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Pulmonary Alveoli, Rats, Rats, Sprague-Dawley, Tetrazoles, Vasodilator Agents, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats. METHODS AND RESULTS: Male Sprague - Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg .kg(-1 ). day(-1)) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p<0.0001). Cilostazol was given to group 2 orally on days 28-90. By day 90 following MCT treatment, the right ventricular (RV) systolic blood pressure and RV hypertrophy were significantly higher in group 1 than in groups 2 and 3 (all values of p<0.01). Additionally, connexin43 and endothelial nitric oxide synthase gene expressions of lung and RV, and Bcl-2 protein expression of RV, were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). Furthermore, the number of alveolar sac and small arterioles of the lung were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). CONCLUSION: Cilostazol therapy effectively attenuates of MCT-induced PAH.