Clin Res Cardiol 96: Suppl 1 (2007)

V104 - Levitra® could be used for the treatment of Pulmonary Hypertension - Preclinical Evidences
 
H. Tinel1, E.-M. Becker1, M. Klein1, J. Hütter1, P. Sandner1
 
1Pharma Research, Bayer Health Care, Wuppertal;
 
Pulmonary Hypertension (PH) is a progressive disease with survival rate less then 2 years after first diagonis. To avoid right heart failure the therapy aim to decrease pulmonary resistance and therefore prostacyclin(IP)-receptor agonists and endothelin antagonists are used. In addition the NO/cGMP system plays an important role in regulation of the vascular tone and it has been shown that the PDE-5 inhibitor Sildenafil is effective in PH.
Our studies aimed to compare the effects of the marketed PDE-5 inhibitors Vardenafil (Levitra®) and Sildenafil (Viagra®) on isolated pulmonary vessels and on pulmonary artery pressure in anaesthetized and conscious dogs.
We investigated the role of Sildenafil and Vardenafil on isolated and pre-contracted mouse pulmonary arteries in vitro. In addition we quantified the effects of Sildenafil and Vardenafil i.v. on pulmonary artery pressure and arterial blood pressure in anaesthetized dogs in vivo. Moreover we measured the effects of Vardenafil i.v. on aortic blood pressure and pulmonary artery pressure in conscious dogs with telemetric implants.
Vardenafil dose-dependently relaxed mouse pulmonary arteries by 30% and 80% at 0.1µM and 1µM respectively. Sildenafil relaxed mouse pulmonary arteries by 20% and 60% at 1µM and 10µM. In the anaesthetized dog model, Vardenafil and Sildenafil i.v. (10µg/kg/h i.v. infusion) decreased pulmonary artery pressure by 30% and 15%, respectively with only moderate effects on systemic blood pressure. In the conscious dog model, Vardenafil (1mg/kg) reduced aortic blood pressure and pulmonary artery pressure at 1mg/kg bolus i.v. by 10% and 20% respectively.
These results demonstrated that Vardenafil and Sildenafil significantly relaxed pulmonary vessels and decreased pulmonary artery pressure in conscious dogs. Since Sildenafil is already approved for therapy, we conclude that Vardenafil might be also useful for the treatment for PH.
 

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