Emerging new uses of phosphodiesterase-5 inhibitors in cardiovascular diseases.

Phosphodiesterase type-5 (PDE-5) is an enzyme that catalyzes the hydrolytic degradation of cyclic GMP - an essential intracellular second messenger that modulates diverse biological processes in living cells. Three selective inhibitors of PDE-5 - sildenafil, vardenafil and tadalafil - have been successfully used by millions of men worldwide for the treatment of erectile dysfunction. Also, sildenafil and tadalafil are currently approved for the treatment of pulmonary hypertension. Recent powerful basic science data and clinical studies suggest potential nonurological applications of PDE-5 inhibitors, including ischemia/reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, stroke, neurodegenerative diseases and other circulatory disorders including Raynaud's phenomenon. Future carefully controlled clinical trials would hopefully expedite their expanding therapeutic use in patients with cardiovascular disease.