The discovery of the nitric oxide/cyclic cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of phosphodiesterase isoenzymes type 5 (PDE5) have been first-line therapy for erectile dysfunction (ED). The success of sildenafil in the treatment of ED stimulated research in the field of PDE5 inhibition and led to many new applications, such as treatment of lower urinary symptoms (LUTS), and pulmonary arterial hypertension, which are now approved indications. However, PDE5 inhibitors have also been used in several other disorders not discussed in this review, and the fields of clinical use are increasing. In the present review the pharmacological basis of the nitric oxide/cyclic cGMP pathway, and the rationale and clinical use of PDE5 inhibitors in different diseases, are discussed.
British journal of pharmacology. 2018 Apr 17 [Epub ahead of print]
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA.