Inhibition of type 5 phosphodiesterase counteracts beta 2-adrenergic signalling in beating cardiomyocytes

Aims Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays a key role in maintaining basal and enhanced contractility stimulated by sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor increases cAMP production, which is countered by the hydrolytic activity of selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP production and hydrolysis modulate downstream signals resulting in different biological responses. The interplay between beta receptors (beta ARs) signalling and phosphodiesterase 5 (PDE5) activity remains to be addressed.