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

• Published in: European journal of clinical investigation Vol. 29; no. 2; pp. 93 - 99
• Main Authors: Sánchez de Miguel, L., De Frutos, T., González-Fernández, F., Del Pozo, V., Lahoz, C., Jiménez, A., Rico, L., García, R., Aceituno, E., Millás, I., Gómez, J., Farré, J., Casado, S., López-Farré, A.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01-02-1999; Blackwell; Blackwell Publishing Ltd
• Subjects: 6-Ketoprostaglandin F1 alpha - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aspirin; Aspirin - pharmacology; Biological and medical sciences; Blotting, Western; Cardiovascular Diseases - drug therapy; Cardiovascular system; Cattle; Cells, Cultured; DNA-Binding Proteins - analysis; Epoprostenol - metabolism; Gene Expression Regulation - drug effects; Interleukin-1 - pharmacology; Medical sciences; Muscle, Smooth - drug effects; NF-kappa B - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; nuclear factor-κB; Pharmacology. Drug treatments; smooth muscle cells; Tumor Necrosis Factor-alpha - metabolism; tumour necrosis factor-α; Vascular wall; Cell culture; Bovine; Enzyme; Cytokine; Antiinflammatory agent; Smooth muscle; Acetylsalicylic acid; In vitro; Biological activity; Nitric-oxide synthase; Myocyte; Vertebrata; Mammalia; Blood vessel; Artiodactyla; Oxidoreductases; Salicylates; Transcription factor NFκB; Transcription factor; Ungulata; Tumor necrosis factor α
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.1999.00425.x

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 1β (IL‐1β, 0.03 U mL−1) induced nitric oxide release by BVSMCs. Aspirin inhibited nitric oxide release from IL‐1β‐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‐κB (NF‐κB). Furthermore, aspirin and the blockade of NO generation by BVSMCs reduced the production of tumour necrosis factor α (TNF‐α) by these cells.
Conclusion
High doses of aspirin inhibited iNOS protein expression in BVSMCs and decreased NF‐κB mobilization. The inhibition of iNOS expression by aspirin was further associated with a reduced ability of BVSMCs to produce TNF‐α. This study could provide new mechanisms of action for aspirin in the treatment of the inflammation‐related cardiovascular diseases.