Cilostazol enhances IL-1β-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway

Abstract Interleukin-1β (IL-1β) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1β-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM–10 μM) potentiated NO production triggered by IL-1β. The mRNA and protein expression of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor of protein kinase A, and N G -monomethyl- l -arginine, an inhibitor of NO synthase, abrogated cilostazol-enhanced IL-1β-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1β-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway.