Phosphodiesterase 5 (PDE5) inhibition, ANP and NO rapidly reduce epididymal duct contractions, but long-term PDE5 inhibition in vivo does not

► PDE5 localizes to smooth muscle, but not to epithelial cells, of the epididymal duct. ► Increase of cGMP by ANP, NO and PDE5 inhibition reduces epididymal duct contractility. ► PDE5 inhibition is additive to ANP and NO effects. ► PDE5 expression is unaltered in a model of long-term PDE5 inhibition in vivo. ► In this model acute cGMP effects on epididymal duct contractility are conserved.