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

Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 microM) potentiated NO production triggered by IL-1beta. 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-1beta-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1beta-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway.