Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double-blind, crossover study.

Abstract

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.

• Authors: Benjamin De Becker, Emeline Hupkens, Laurence Dewachter, Catherine Coremans, Cédric Delporte, Pierre van Antwerpen, Thierry Franck, Karim Zouaoui Boudjeltia, Pierre Cullus, Philippe van de Borne
• Journal: Physiological reports (Physiol Rep) Vol. 9 Issue 17 Pg. e15018 (09 2021) ISSN: 2051-817X [Electronic] United States
• PMID: 34435469 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Gout Suppressants
• Febuxostat
• Uric Acid

Topics

• Adult
• Aged
• Blood Pressure (physiology)
• Cross-Over Studies
• Double-Blind Method
• Endothelium, Vascular (drug effects, metabolism)
• Febuxostat (pharmacology)
• Female
• Forearm (blood supply, physiology)
• Gout Suppressants (pharmacology)
• Humans
• Laser-Doppler Flowmetry (methods)
• Male
• Middle Aged
• Oxidative Stress (drug effects, physiology)
• Uric Acid (blood)
• Vascular Stiffness (physiology)