Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Growing evidence indicate that Rheumatoid Arthritis (RA)-associated increase in cardiovascular risk is secondary to the presence of endothelial dysfunction (ED). Although Tumor Necrosis Factor inhibitors are unanimously approved for the treatment of RA, their effect on ED is still controversial. The present study aimed to determine the impact of etanercept on ED as well as the mechanisms involved in the model of adjuvant-induced arthritis (AIA) rats.
Methods
AIA was induced by an intradermal injection of Mycobacterium butyricum in the tail of male Lewis rats. At the first signs of arthritis, AIA rats received etanercept (10 mg/kg/ 3 days, s.c) or saline (controls AIA) for 21 days. Arthritis score was daily evaluated. At the end of experiment, preconstricted isolated aortic rings were relaxed with acetylcholine (Ach, 10-11-10-4moles/liter) in the presence or not of inhibitor of nitric oxide (NO) synthase (L-NAME), cyclooxygenase-2 (NS398), arginase (nor-NOHA), endothelium-derived hyperpolarizing factor (EDHF) (apamin/charybdotoxin) and superoxide anions production (Tempol). Blood pressure was measured by invasive method.
Results
Compared to controls AIA, etanercept significantly reduced arthritis score (-34%, p<0.001). This was associated with an improvement of Ach-induced relaxation (p<0.05). These beneficial effects of etanercept on ED were mediated by a decrease in cyclooxygenase-2 and arginase activity, a decrease in superoxide anions production and an increase in NO synthase activity. EDHF production was unaffected by the treatment. Surprisingly, no correlation was found between the arthritis score and Ach-induced relaxation (Emax) (r=-0.195; p=0.246). Last, etanercept significantly increased systolic blood pressure (125.2 ± 5.7 vs 107.1 ± 5.5 controls AIA, p<0.05), but not diastolic blood pressure.
Conclusion
Our study demonstrated that etanercept decreases endothelial dysfunction in conduit arteries despite increasing blood pressure. The beneficial effects involved the modulation of vascular NO synthase, cyclooxygenase-2, arginase and superoxide anions production pathways. Our data suggested that these effects are, at least in part, independent on arthritis severity reduction.
Disclosure:
P. Totoson,
None;
K. Maguin-Gaté,
None;
D. Wendling,
None;
C. Demougeot,
None.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-etanercept-on-endothelial-dysfunction-in-rat-adjuvant-induced-arthritis/