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


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.


CONCLUSIONS
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.
Sánchez de Miguel
L
L
Nephrology, Hypertension and Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain.
de Frutos
T
T
González-Fernández
F
F
del Pozo
V
V
Lahoz
C
C
Jiménez
A
A
Rico
L
L
García
R
R
Aceituno
E
E
Millás
I
I
Gómez
J
J
Farré
J
J
Casado
S
S
López-Farré
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis; D011464:Epoprostenol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001241:Aspirin