Abstract 17175: Phoshodiesterase 2 - A New Member Of Proteins Involved In Beta-adrenergic Desensitization

Diminished cAMP- and augmented cGMP-signaling is characteristic for failing hearts. Among the PDE superfamily, phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, but primarily hydrolysis cAMP. This appears to mediate a negative cross-talk between cAMP- and cGMP signaling pathways. However, the role of PDE2 in the heart is only poorly understood. Here, we investigated whether myocardial PDE2 is altered in heart failure (HF) and determined PDE2 mediated effects in isolated cardiomyocytes, in a cardiac stress model as well as in PDE2 heart-specific transgenic mice (TGs). Immunoblotting revealed that myocardial left-ventricular PDE2 expression was ~2-fold higher in patients with end-stage heart failure. Accordingly, chronic beta-AR stimulation via isoprenaline infusions in rats induced a similar increase in PDE2 expression accompanied by an enhanced PDE2 cAMP hydrolytic activity of 4-fold compared to NaCl-controls. Cardiomyocytes isolated from this model showed blunted cardiac beta-A...