PDE5 Inhibition Counteracts beta-Adrenergic Induction Of Cardiac Hypertrophy

The beta-adrenoreceptors play important roles in cardiovascular function regulation mediated by the sympathetic nervous system. It is known that sustained beta-adrenergic stimulations promotes cardiac hypertrophy. Recently, an anti-hypertrophic role of sildenafil, that acts as a specific phosphodiesterase 5 (PDE5) inhibitor, has been demonstrated in mice where hypertrophy was mechanically induced. We report the results obtained on an in vitro model of cardiac hypertrophy. By using three-dimensional cultures of mouse ventricular cardiomyocytes we show that: 1) these cells express levels of PDE5 comparable with the ones in normal heart, 2) treatment of the cultures with the beta-adrenoreceptors agonist isoproterenol induces cell hypertrophy accompanied by an increment of the level of PDE5 expression and 3) sildenafil prevents the development of such hypertrophy. In summary, we present a test system that may contribute to clarify intracellular signaling pathways leading to cardiac hypertrophy and to identify molecular targets, like the ones involved in PDE5 activity, on which to steer the development of new drugs and to design new clinical therapies.