[en] We hypothesized acute moderate and drastic reductions in uric acid concentration exert different effects on arterial function in healthy normotensive and hypertensive adults. Thirty-six adults (aged 58 [55;63] years) with or without primary hypertension participated in a three-way, randomized, double-blind, crossover study in which [placebo] and [febuxostat] and [febuxostat and rasburicase] were administered. Febuxostat and rasburicase reduce the uric acid concentration by xanthine oxidoreductase inhibition and uric acid degradation into allantoin, respectively. Endothelial function was assessed in response to acetylcholine, sodium nitroprusside, heating (with and without nitric oxide synthase inhibition) using a laser Doppler imager. Arterial stiffness was determined by applanation tonometry, together with blood pressure, renin-angiotensin system activity, oxidative stress, and inflammation. Uric acid concentration was 5.1 [4.1;5.9], 1.9 [1.2;2.2] and 0.2 [0.2;0.3] mg/dL with [placebo], [febuxostat] and [febuxostat-rasburicase] treatments, respectively (p < 0.0001). Febuxostat improved endothelial response to heat particularly when nitric oxide synthase was inhibited (p < 0.05) and reduced diastolic and mean arterial pressure (p = 0.008 and 0.02, respectively). The augmentation index decreased with febuxostat (ANOVA p < 0.04). Myeloperoxidase activity profoundly decreased with febuxostat combined with rasburicase (p < 0.0001). When uric acid dropped, plasmatic antioxidant capacity markedly decreased, while superoxide dismutase activity increased (p < 0.0001). Other inflammatory and oxidant markers did not differ. Acute moderate hypouricemia encompasses minor improvements in endothelial function, blood pressure, and arterial stiffness. Clinical Trial Registration: NCT03395977, https://clinicaltrials.gov/ct2/show/NCT03395977.
Disciplines :
General & internal medicine
Author, co-author :
De Becker, Benjamin ; Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Hupkens, Emeline; Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
Dewachter, Laurence; Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
Coremans, Catherine; RD3 - Pharmacognosy, Bioanalysis and Drug Discovery & Analytical Platform of the Faculty of Pharmacy (APFP), Faculty of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium
Delporte, Cédric; RD3 - Pharmacognosy, Bioanalysis and Drug Discovery & Analytical Platform of the Faculty of Pharmacy (APFP), Faculty of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium
van Antwerpen, Pierre; RD3 - Pharmacognosy, Bioanalysis and Drug Discovery & Analytical Platform of the Faculty of Pharmacy (APFP), Faculty of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium
Franck, Thierry ; Université de Liège - ULiège > Centres généraux > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Zouaoui Boudjeltia, Karim; Laboratory of Experimental Medicine (ULB 222), Medicine Faculty, Université Libre de Bruxelles, CHU de Charleroi, Hopital Vesale, Montigny-le-Tilleul, Belgium
Cullus, Pierre; Biostatistics department, Medicine Faculty, Université Libre de Bruxelles, Brussels, Belgium
van de Borne, Philippe; Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Language :
English
Title :
Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double-blind, crossover study.
Erasme University Hospital [BE] KBS - Koning Boudewijnstichting [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
DE BECKER Benjamin is a Research Fellow – Fonds National de la Recherche Scientifique (FNRS, Belgium). This work was supported by Grants from the “Fonds National de la Recherche Scientifique” (30309647, 34735921 to B.D.B and 31292322 to Ph.v.d.B.); “Docteur et Madame René Tagnon” fund; the “Fonds pour la Chirurgie Cardiaque”; and the “Fonds Erasme” from the Erasme Hospital-ULB, Brussels, Belgium. The Analytical Platform of the Faculty of Pharmacy (ULB) is supported by Fonds National de la Recherche Scientifique (FNRS, Belgium) and ULB Platform. The authors express their gratitude to the “Fonds National de la Recherche Scientifique” (Belgium), the “Docteur et Madame René Tagnon” Fund (Belgium), the “Fonds pour la Chirurgie Cardiaque” (Belgium) and the “Fonds Erasme,” Erasme Hospital-ULB, Brussels (Belgium). The authors thank all the participants for their participation and Mrs VANDESMAL Estel for the management of pharmaceutical products. Editorial assistance, in the form of language editing and correction, was provided by XpertScientific Editing and Consulting.DE BECKER Benjamin is a Research Fellow – Fonds National de la Recherche Scientifique (FNRS, Belgium). This work was supported by Grants from the “Fonds National de la Recherche Scientifique” (30309647, 34735921 to B.D.B and 31292322 to Ph.v.d.B.); “Docteur et Madame René Tagnon” fund; the “Fonds pour la Chirurgie Cardiaque”; and the “Fonds Erasme” from the Erasme Hospital‐ULB, Brussels, Belgium. The Analytical Platform of the Faculty of Pharmacy (ULB) is supported by Fonds National de la Recherche Scientifique (FNRS, Belgium) and ULB Platform.
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