J Korean Soc Vasc Surg.  2004 May;20(1):24-29.

Suppression of iNOS Expression by NSAIDs and Acetaminophen in Vascular Smooth Muscle Cells

• Jo HJ
• Choi HC
• Lee KY
• Ha JH
• Jo HC

Abstract

PURPOSE
iNOS expression in vascular smooth muscle cells (VSMC) causes the development of septic shock, and multiple organ dysfunction syndrome (MODS). For the inhibition of iNOS expression, glucocorticoids are known to inhibit iNOS expression but immunosuppression decreases its clinical availability. Recently, aspirin was reported to inhibit iNOS expression, but the mechanism and effectiveness are still unclear. In this investigation, on aspirin, several non steroidal antiinflammatory drugs (NSAIDs) were applied to clarify the inhibitory mechanism of iNOS expression and NO production in lipopolysaccharide (LPS) treated VSMCs. METHOD: VSMCs were primarily cultured from rat aorta and confirmed by immunocytochemistry of anti-smooth muscle myosin antibody. LPS, an inducer of iNOS, and NSAIDs, such as aspirin, indomethacin, ketoprofen sodium salicylate and acetaminophen were used. The concentrations of nitrite in culture media following the addition of LPS with a 1-hour pretreatment of NSAIDs were measured by spectrophotometry with griess reaction. Western blot and RT-PCR for iNOS protein and iNOS mRNA, respectively, were performed. RESULT: Acetaminophen had no effect on the inhibition of nitrite production. NSAIDs, especially ketoprofen and sodium salicylate, showed a significant inhibitory effect on nitrite production. In their mechanism, all the NSAIDs in present study inhibited iNOS mRNA and protein expression.
CONCLUSION
These results suggest that the inhibitory mechanism on iNOS expression of NSAIDs is due to the inhibition of iNOS mRNA expression and subsequent inhibition of iNOS protein expression.

Keyword

LPS; iNOS; NSAIDs; Acetaminophen

MeSH Terms

Acetaminophen*
Animals
Anti-Inflammatory Agents, Non-Steroidal*
Aorta
Aspirin
Blotting, Western
Culture Media
Glucocorticoids
Immunohistochemistry
Immunosuppression
Indomethacin
Ketoprofen
Multiple Organ Failure
Muscle, Smooth, Vascular*
Myosins
Rats
RNA, Messenger
Shock, Septic
Sodium Salicylate
Spectrophotometry
Acetaminophen
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Culture Media
Glucocorticoids
Indomethacin
Ketoprofen
Myosins
RNA, Messenger
Sodium Salicylate