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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

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

U Ikeda1, M Shimpo, Y Murakami

  • 1Department of Cardiology, Jichi Medical School, Tochigi, Japan. uikeda@jichi.ac.jp

Hypertension (Dallas, Tex. : 1979)
|June 17, 2000
PubMed

Insights

Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands reduce nitric oxide (NO) synthesis in vascular cells. This finding suggests PPARgamma agonists may impact atherosclerosis and restenosis development.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Endocrinology

Background:

  • Peroxisome proliferator-activated receptor-gamma (PPARgamma) is crucial for glucose metabolism.
  • PPARgamma ligands' role in vascular nitric oxide (NO) synthesis is implicated in plaque formation and restenosis.
  • Investigating PPARgamma's influence on vascular smooth muscle cell NO production is essential.

Purpose of the Study:

  • To examine the effects of PPARgamma ligands on nitric oxide (NO) synthesis in vascular smooth muscle cells.
  • To determine if PPARgamma agonists can modulate NO production stimulated by inflammatory cytokines.
  • To explore the molecular mechanisms underlying PPARgamma's regulation of NO synthesis in vascular cells.

Main Methods:

  • Cultured rat vascular smooth muscle cells were stimulated with interleukin-1beta.
  • Nitrite production (a stable NO metabolite) was measured.
  • PPARgamma agonists (troglitazone, 15d-PG J(2)) were used to assess their inhibitory effects.
  • Inducible NO synthase (iNOS) mRNA and protein levels were quantified.
  • Nuclear factor-kappaB (NF-kappaB) activation was analyzed.

Main Results:

  • Interleukin-1beta significantly increased nitrite production in vascular smooth muscle cells.
  • PPARgamma agonists, troglitazone and 15d-PG J(2), dose-dependently inhibited this nitrite production.
  • The inhibition of nitrite production correlated with decreased iNOS mRNA and protein.
  • Both agonists suppressed interleukin-1beta-induced nuclear factor-kappaB activation.

Conclusions:

  • PPARgamma ligands inhibit NO synthesis in cytokine-stimulated vascular smooth muscle cells.
  • These findings suggest a direct vascular smooth muscle action of PPARgamma agonists.
  • PPARgamma agonists may influence the pathogenesis of atherosclerosis and restenosis.

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