Concentration-dependent differential effects of udenafil on viability, proliferation, and apoptosis in vascular endothelial and smooth muscle cells

Objectives: Local strategies directed against vascular smooth muscle cell (VSMC) proliferation, such as drug-eluting stents (DES), reduce the occurrence of restenosis. However, these approaches may also inhibit vascular endothelial cell (VEC) proliferation and impair reendothelialization, and hence, increase susceptibility to late thrombosis. In this study we examined the differential effects of various concentrations of the type 5 phosphodiesterase (PDE-5) inhibitor, udenafil, on viability, proliferation, and apoptosis of VEC and VSMC, in order to identify the optimal concentration of udenafil that minimizes inhibition of VEC survival and growth, and maximizes inhibition of VSMC survival and growth. Materials and Methods: VEC from human umbilical veins and VSMC from human aorta were exposed to various concentrations of udenafil (1, 10, and 100 mu mol/l and 1 mmol/l) for 24 h, and its effects on cell viability, proliferation, and apoptosis were studied using 5-bromo-2'-deoxyuridine (BrdU), methylthiazoletetrazolium (MTT) assay, trypan blue dye exclusion, and flow cytometry. Results: Udenafil inhibited the survival and growth of VEC and VSMC in a concentration-dependent manner over a range of concentrations. At 100 mu mol/l, udenafil, inhibited VEC proliferation significantly less than VSMC proliferation (P < 0.05), and could significantly induce VEC apoptosis less than VSMC apoptosis (P < 0.05). Conclusions: Udenafil has a differential effect on survival and growth in VEC and VSMC. The maximal differential effect, with minimal inhibition of VEC and maximal inhibition of VSMC, occurs at 100 mu mol/l. This characteristic suggests that udenafil is a promising agent for use in DES.