Improvement of exercise capacity in monocrotaline-induced pulmonary hypertension by the phosphodiesterase-5 inhibitor Vardenafil

Abstract

Vardenafil, a phosphodiesterase-5 inhibitor, is approved for the therapy of erectile dysfunction. However, in contrast to Sildenafil and Tadalafil, little is known about its effects on pulmonary hypertension. Four weeks after monocrotaline-administration rats exhibited a significant increase in right ventricular pressure (RVSP, 94mmHg vs. 25mmHg; p=0.001) right ventricular weight (right ventricle/left ventricle+septum, 59 vs. 23; p=0.001) and pulmonary vascular remodeling (medial wall area 104% vs. 66%; p<0.05) as compared to controls, with a corresponding reduction in exercise capacity (% from baseline value: 67%; p<0.05). Vardenafil treatment resulted in decreased RVSP (56mmHg vs. 95mmHg; p=0.008), right ventricular weight (41 vs. 59; p=0.013), pulmonary vascular remodeling (medial wall area 64% vs. 104%; p<0.05) and a significant better exercise capacity (% from baseline value: 84% vs. 67%; p<0.05) compared to monocrotaline only treated animals. In conclusion, Vardenafil exerts beneficial effects on monocrotaline-induced pulmonary hypertension in rats. Whether it is a treatment option for patients with pulmonary hypertension needs to be elucidated.