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(Hypertension. 2000;35:1232.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Peroxisome Proliferator–Activated Receptor- Ligands Inhibit Nitric Oxide Synthesis in Vascular Smooth Muscle Cells

Uichi Ikeda; Masahisa Shimpo; Yoshiaki Murakami; Kazuyuki Shimada

From the Department of Cardiology, Jichi Medical School, Tochigi, Japan.

Correspondence to Uichi Ikeda, MD, PhD, Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Tochigi 329-0498, Japan. E-mail uikeda{at}jichi.ac.jp

Abstract—Peroxisome proliferator–activated receptor- (PPAR) is a key player in glucose metabolism. If PPAR 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 ligands on NO synthesis in vascular smooth muscle cells. Incubation of cultures with interleukin-1ß (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 agonists troglitazone and 15-deoxy-^12,14-prostaglandin J₂ (15d-PG J₂) dose-dependently inhibited nitrite production by interleukin-1ß–stimulated vascular smooth muscle cells. Decreased interleukin-1ß–induced nitrite production by the PPAR agonists was accompanied by decreased inducible NO synthase mRNA and protein accumulation. Interleukin-1ß induced nuclear factor-B activation in vascular smooth muscle cells, and both troglitazone and 15d-PG J₂ markedly suppressed this nuclear factor-B activation. PPAR 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.

Key Words: interleukins • nitric oxide • muscle, smooth • atherosclerosis

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