Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

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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 endothe-lial 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 (75mg/kg) only (group 1), MCT plus cilostazol (20mg-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.
社団法人日本循環器学会の論文
2008-04-20

Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

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