Frank Verhoeven1, Perle Totoson2, Christine Marie3, Anne Prigent-Tessier3, Daniel Wendling4, Maude Tournier-Nappey2, Clément Prati1, Céline Demougeot5. 1. PEPITE EA4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030, Besançon, France; Service de Rhumatologie, CHRU Besançon, 25000 Besançon, France. 2. PEPITE EA4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030, Besançon, France. 3. INSERM U1093, Univ. Bourgogne Franche-Comté, F-21000, Dijon, France. 4. Service de Rhumatologie, CHRU Besançon, 25000 Besançon, France; EA4266, Univ. Bourgogne Franche-Comté, F-25030, Besançon, France. 5. PEPITE EA4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030, Besançon, France. Electronic address: cdemouge@univ-fcomte.fr.
Abstract
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.
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.
Authors: Emanuela Ricciotti; Cecilia Castro; Soon Yew Tang; William T E Briggs; James A West; Dania Malik; Seth D Rhoades; Hu Meng; Xuanwen Li; Nicholas F Lahens; Jeffrey A Sparks; Elizabeth W Karlson; Aalim M Weljie; Julian L Griffin; Garret A FitzGerald Journal: Circulation Date: 2018-11-20 Impact factor: 29.690
Authors: Arduino A Mangoni; Richard J Woodman; Matteo Piga; Alberto Cauli; Anna Laura Fedele; Elisa Gremese; Gian Luca Erre Journal: Front Cardiovasc Med Date: 2021-07-19