Therapeutic potential of phosphodiesterase 5 inhibition for cardiovascular disease

Pharmacological inhibition of PDE 5 exhibits differential effects in different organs according to its expression in various tissues. Therapeutic doses of sildenafil, used in the treatment of male erectile dysfunction, exhibit slight blood pressure-lowering effects and do not appear to compromise coronary blood flow in coronary artery disease. However, the combination of sildenafil with any agent serving as a nitric oxide donor is contraindicated because of potentially life-threatening hypotension. Despite theoretical concerns of promoting cardiac arrhythmia and reducing myocardial tolerance to ischemia, the risk for a cardiac event with sildenafil treatment is not higher than what would be expected for the population of patients treated for erectile dysfunction, characterized by several coronary risk factors. In patients with pulmonary hypertension of various etiologies, treatment with sildenafil is promising and may provide the unique opportunity of improving the efficacy of inhalative agents, leading to site-specific, additive, or overadditive effects. In addition, further investigations of the effect of PDE 5 inhibition in diseases associated with endothelial dysfunction seem to be worthwhile, as PDE 5 inhibition could favorably influence abnormal vasomotion caused by compromised endothelial nitric oxide release. Neurological, ophthalmological, or gastroenterological side effects require further investigations, even if their incidence might be low and a causal connection has not yet been proven.