Peroxisome proliferator-activated receptor-gamma ligands inhibit nitric oxide synthesis in vascular smooth muscle cells

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a key play er in glucose metabolism. If PPAR gamma ligands modulate nitric oxide (NO) synthesis in the vascular tissue, they may affect the process of plaque for mation and postangioplasty restenosis, We investigated the effects of PPAR gamma ligands on NO synthesis in vascular smooth muscle cells. Incubation o f cultures with interleukin-1 beta (10 ng/mL) for 24 hours caused a signifi cant increase in the production of nitrite, a stable metabolite of NO, in c ultured rat vascular smooth muscle cells. The PPAR gamma agonists troglitaz one and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PG J(2)) dose-depende ntly inhibited nitrite production by interleukin-1 beta-stimulated vascular smooth muscle cells. Decreased interleukin-1 beta-induced nitrite producti on by the PPAR gamma agonists was accompanied by decreased inducible NO syn thase mRNA and protein accumulation. Interleukin-1 beta induced nuclear fac tor-kappa B activation in vascular smooth muscle cells, and both troglitazo ne and 15d-PG J(2) markedly suppressed this nuclear factor-kappa B activati on. PPAR gamma ligands inhibit NO synthesis in cytokine-stimulated vascular smooth muscle cells, suggesting that these agonists may act directly on th e vascular smooth muscle and influence the process of atherosclerosis and r estenosis.