Clinical and histopathological relationship of sildenafil and bosentan treatments in rats with monocrotaline induced pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a challenging disorder characterized by increasing pulmonary artery pressure, which is hard to treat.

Objective: This study was aimed to investigate the effects of bosentan, sildenafil and their combination.

Methods: Saline or MCT were applied to Wistar rats. By the development of PAH (4th week), MCT-given rats were treated orally with bosentan, sildenafil and combination of sildenafil and bosentan or placebo. ECHO examinations were performed. Tissues obtained from all of the rats were evaluated under an electron microscope.

Results: Left ventricular end diastolic diameter significantly increased in sildenafil and combined groups. Sildenafil group revealed a significant decrease in RV pressure and wall thickness. Examination of lung revealed a significant amount of connective tissue formation and increase in inflammatory cells in all the groups except controls in the interalveolar septum. Examination of PA revealed an increase in connective tissue volume, hypertrophic changes and expansions in granular endoplasmic reticulum cisternaes in smooth muscle cells in active groups rather than in the controls. Unlike the controls, the examination of the RV revealed an enlargement of the sarcoplasmic reticulum cisternaes in some cells, due to the calcium increase.

Conclusion: Sildenafil and the combined therapy demonstrated to have more impact on pressure and the RV parameters in rats, with lower inflammatory findings in lung tissue (Fig. 6, Ref. 31).