Sildenafil Reduces Inflammation and Prevents Pulmonary Arterial Remodeling of the Monocrotaline - induced Disease in the Wistar Rats.

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Abstract
Pulmonary arterial hypertension (PAH) is a rare and severe disease with incompletely under stood pathogenesis. PAH is associated with pulmonary arterial remodeling and inflammation. We evaluated the effects of Sildenafil on the Monocrotaline (MCT) -induced disease in Wistar rats, for potential benefit in the early phases of inflammation and vascular remodeling. MCT-injected rats, MCT-injected sildenafil-treated rats (starting day 1 with 2 x 0.2 mg/day; total of 2 mg/kgc/day) and saline-injected control rats were evaluated at day 14 and day 28 following MCT for pulmonary morphological changes - lesions, inflammation (inflammator y index), arterial morphometry (hypertrophy index), immunohistochemistry for smooth muscle cell marker. The administration of sildenafil following MCT significantly reduced the severity of inflammation in the acute stage of the disease (reduction of the inflammatory index by 6.038% (p <0.05)) and prevented pulmonary arterial remodeling (reduction of the hypertrophy index by 7.306% (p<0.001)). It also improved survival in the early phase with a mortality rate during the first 14 days of 4 in the MCT- exposed rats vs 1 in the MCT-exposed sildenafil-treated rate. Early administration of sildenafil in the MCT experimental PAH improves inflammation and survival, and prevents pulmonary vascular remodeling. Our study suggests that one of the mechanisms involved, besides vasodilatation and anti-proliferative effect, could be a direct anti-inflammatory effect of sildenafil.

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