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

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a key player in glucose metabolism. If PPAR gamma ligands modulate nitric oxide (NO) synthesis in the vascular tissue, they may affect the process of plaque formation and postangioplasty restenosis, We investigated the effects of PPAR gamma ligands on NO synthesis in vascular smooth muscle cells. Incubation of cultures with interleukin-1 beta (10 ng/mL) for 24 hours caused a significant increase in the production of nitrite, a stable metabolite of NO, in cultured rat vascular smooth muscle cells. The PPAR gamma agonists troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PG J(2)) dose-dependently inhibited nitrite production by interleukin-1 beta-stimulated vascular smooth muscle cells. Decreased interleukin-1 beta-induced nitrite production by the PPAR gamma agonists was accompanied by decreased inducible NO synthase mRNA and protein accumulation. Interleukin-1 beta induced nuclear factor-kappa B activation in vascular smooth muscle cells, and both troglitazone and 15d-PG J(2) markedly suppressed this nuclear factor-kappa B activation. PPAR gamma ligands inhibit NO synthesis in cytokine-stimulated vascular smooth muscle cells, suggesting that these agonists may act directly on the vascular smooth muscle and influence the process of atherosclerosis and restenosis.