Acute effects of phosphodiesterase 5 (PDE5) inhibition, ANP and NO on epididymal contractility are preserved despite chronic PDE5 exposure

Background To acquire motility and their fertilizing capacity, immotile spermatozoa have to transit from the testis through the epididymal duct to the distal parts of the organ where spermatozoa are stored until ejaculation. This transit mainly relies on contractions of the epididymal peritubular smooth muscle layer and various factors, including cGMP, contribute to its fine regulation [1,2]. Atrial natriuretic peptide (ANP) and nitric oxide (NO) affect contractility via cGMP-dependent pathways. Phosphodiesterases (PDEs) hydrolyzing cGMP control intracellular cGMP levels and thus limit a given cGMP signal. Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. Besides its use for the treatment of erectile dysfunction, sildenafil has gained importance as a therapeutic agent against pulmonary hypertension. Thus, an increasing number of young patients is exposed to chronic PDE5 inhibition. Currently, there is still very little knowledge about the occurrence and functional importance of PDEs in the epididymis and more specifically about possible effects or side effects of sildenafil on epididymal function.