Novel effect of sildenafil on hair growth

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. However, the effect of sildenafil on human hair follicles (hHFs) is unknown. The purpose of this study was to determine the role of sildenafil in hair growth. We investigated the expression of PDE5 in human dermal papilla cells (hDPCs) and hHFs. The effects of sildenafil on hDPC proliferation were evaluated using BrdU assays. The mRNA expression of growth factors and extracellular signal-regulated kinase (ERK) phosphorylation were investigated using real-time PCR and western blotting, respectively. Additionally, anagen induction and perifollicular vessel formation were evaluated using an in vivo mice model. We confirmed high expression of PDE5 in hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice. Our study demonstrates for the first time, the significant therapeutic potential of sildenafil on hair growth and its potential use in treatment of alopecia.