Diclofenac but not celecoxib improves endothelial function in rheumatoid arthritis: A study in adjuvant-induced arthritis.

BACKGROUND AND AIMS: We aimed at investigating the effect of celecoxib (COX-2 selective inhibitor) and diclofenac (non-selective COX inhibitor) on endothelial function, and at identifying the underlying mechanisms in adjuvant-induced arthritis (AIA).

METHODS

At the first signs of AIA, diclofenac (5 mg/kg twice a day, i.p), celecoxib (3 mg/kg/day, i.p) or saline (Vehicle) was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of NOS, arginase, EDHF and superoxide anions (O2-°) production. Aortic expression of eNOS, Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, glycaemia and serum ADMA levels were measured.

RESULTS

Diclofenac and celecoxib significantly reduced arthritis score to the same extent (p<0.05). As compared to vehicle-treated AIA, celecoxib did not change whereas diclofenac improved endothelial function (p<0.05) through increased EDHF production, decreased arginase activity and expression, decreased superoxide anions production and expression of p22phox and p47phox. Diclofenac but not celecoxib significantly enhanced blood pressure and serum ADMA levels. Glycaemia was unchanged by both treatments.

CONCLUSIONS

Our study reveals that the effect of NSAIDs on endothelial function cannot be extrapolated from their impact on arthritis severity and suggest that changes in blood pressure and plasma ADMA levels may not be useful to predict CV risk of NSAIDs in RA.