Aspirin inhibits inducible nitric oxide synthase expression and tumour necrosis factor-alpha release by cultured smooth muscle cells

Eur J Clin Invest. 1999 Feb;29(2):93-9. doi: 10.1046/j.1365-2362.1999.00425.x.

Abstract

Background: Inflammatory related cardiovascular disease, i.e. cardiac allograft rejection, myocarditis, septic shock, are accompanied by cytokine production, which stimulates the expression of inducible nitric oxide (iNOS).

Materials and methods: The aim of the present study was to examine whether anti-inflammatory doses of acetylsalicylic acid (aspirin) could regulate iNOS protein expression in bovine vascular smooth muscle cells (BVSMCs) in culture.

Results: Interleukin 1 beta (IL-1 beta, 0.03 U mL-1) induced nitric oxide release by BVSMCs. Aspirin inhibited nitric oxide release from IL-1 beta-stimulated BVSMCs in a dose-dependent manner. In addition, aspirin significantly inhibited iNOS protein expression in BVSMCs and reduced the translocation of the nuclear factor-kappa B (NF-kappa B). Furthermore, aspirin and the blockade of NO generation by BVSMCs reduced the production of tumour necrosis factor alpha (TNF-alpha) by these cells.

Conclusion: High doses of aspirin inhibited iNOS protein expression in BVSMCs and decreased NF-kappa B mobilization. The inhibition of iNOS expression by aspirin was further associated with a reduced ability of BVSMCs to produce TNF-alpha. This study could provide new mechanisms of action for aspirin in the treatment of the inflammation-related cardiovascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • Blotting, Western
  • Cardiovascular Diseases / drug therapy
  • Cattle
  • Cells, Cultured
  • DNA-Binding Proteins / analysis
  • Epoprostenol / metabolism
  • Gene Expression Regulation / drug effects
  • Interleukin-1 / pharmacology
  • Muscle, Smooth / drug effects*
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • DNA-Binding Proteins
  • Interleukin-1
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • 6-Ketoprostaglandin F1 alpha
  • Epoprostenol
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Aspirin