Background/Purpose: Rheumatoid Arthritis (RA) is associated to an increase of cardiovascular (CV) risk explained in part by an accelerated atherosclerosis as a consequence of endothelial dysfunction. Glucocorticoids (GCs) are widely prescribed in RA patients. Surprisingly, despite the commonly held belief that glucocorticoids worsen the CV risk, data concerning their impact on endothelial function in RA are lacking. The present study investigate the effect of prednisolone on vascular function in arthritic rats and identified the underlying mechanisms.

Methods : Adjuvant-induced arthritis (AIA) was induced in 6 weeks old male Lewis rats by injection of Mycobacterium butyricum in adjuvant at the basis of the tail. At the onset of arthritis, rats were daily treated (i.p) with prednisolone at 10 (high dose) or 0.1 mg / kg (Low dose) or saline (Vehicle) for 21 days. Arthritis score and tarsus diameter were daily monitored. At the end of treatment, thoracic aortas were harvested to measure the relaxation to acetylcholine on pre-constricted aortic rings in the presence or not of inhibitor of nitric oxide (NO) synthase (L-NAME), arginase (nor-NOHA), COX-2 (NS-398), EDHF (Apamin/Charybdotoxin), or a superoxide dismutase analog (Tempol). The relaxing effect of a NO donor (sodium nitroprussiate, SNP) was studied on endothelium-denuded aortic rings. Blood pressure and heart rate, glycaemia, triglyceride and total cholesterol levels and radiological score of hind paws were also assessed.

Results: Compared to “Vehicle”, AIA “High dose” exhibited reduced (p<0.05) arthritic score, paw diameters and radiological damage. This dose of GC significantly (p<0.05) improved Ach-induced relaxation through increased NO synthase activity and EDHF production, decreased arginase and COX-2 activities and decreased superoxide anions production. Blood pressure and triglyceride level were significantly (p<0.05) higher in AIA “high dose”. By contrast, the low dose of prednisolone modified nor arthritis severity neither blood pressure, glycaemia and triglycerides levels. On the vascular side, this dose decreased the production of superoxide anions and increased EDHF, but failed to improve endothelial function in AIA rats. The response of rings to the NO donor was unchanged after GC treatment whatever the dose.

Conclusion: Our study demonstrates for the first time that a high dose of prednisolone during a short time is beneficial for endothelial function in case of arthritis, even though it induced deleterious cardio-metabolic effects. From a clinical perspective, these results raise the question of the use of high doses of GC during a short period to reverse endothelial dysfunction along with a rapid disease control. Whether this beneficial vascular effect of GC depends on the reduction of disease activity or not deserves further investigations.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/glucocorticoids-and-vascular-function-in-arthritis-benefic-or-deleterious-effects-study-in-rat/