Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure?

Phosphodiesterase type 5 (PDE5) is an enzyme that belongs to a large family of cyclic nucleotide PDEs that catalyze cAMP and cGMP. cAMP and cGMP are 2 essential intracellular second messengers regulating many different cellular functions of living cells. PDE5 specifically breaks down the substrate cGMP. Inhibition of PDE5 increases intracellular cGMP levels by inhibiting its degradation. Sildenafil (Viagra) is a potent and selective inhibitor of cGMPspecific PDE5 and is the first oral treatment for men with erectile dysfunction; it was approved by Food and Drug Administration on March 27, 1998. Sildenafil binds to the catalytic site of PDE5 and inhibits the degradation of intracellular cGMP in smooth muscle within the corpus cavernosum, resulting in increased levels of cGMP, which cause smooth muscle cell relaxation and vasodilation and improve erectile function.1,2