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Sildenafil, approved two decades ago, is the inhibitor of phosphodiesterase 5 (PDE5). First of all, it was designated for angina pectoris, but soon it showed a wonderful efficacy in erectile dysfunction (ED) and then pulmonary arterial hypertension (PAH). Due to the distribution of phosphodiesterase (PDE) in almost all organs, maybe it effects other diseases. Hence, a great number of investigations began to understand the role of PDEi in different organs. Preliminary research on sildenafil in cell culture and animal models has yielded promising results. Soon, a greater number of animal researches and clinical trials joined them. The results disclosed sildenafil can have beneficial effects in each organ such as heart, liver, kidney, brain, and intestines. Furthermore, it has significantly improved the prognosis of organ ischemia in various animal models. Clinical trials in several diseases, such as recurrent spontaneous miscarriage, fatty liver disease, bronchopulmonary dysplasia (BPD), heart failure, and premature ejaculation (PE) brought promising results. Although some clinical trials are available on the effects of sildenafil on various diseases, further studies on humans are needed to consolidate the ultimate effects of sildenafil. The aim of this review was to describe the effects of sildenafil on each organ and explain its mechanisms of action. Further, other PDE inhibitors such as tadalafil and vardenafil have been briefly discussed in parts of this review.

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