ArticleNaunyn-Schmiedeberg's archives of pharmacology2016
Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Efficacy and safety of urate-lowering therapies in asymptomatic hyperuricaemia: a systematic review and network meta-analysis of key clinical outcomes.Annals of medicine · 2025Pooled it
- Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study.Clinical cardiology · 2023Trial
- A randomized, double-blind, positive-controlled, prospective, dose-response clinical study to evaluate the efficacy and tolerability of an aqueous extract of Terminalia bellerica in lowering uric acid and creatinine levels in chronic kidney disease subjects with hyperuricemia.BMC complementary medicine and therapies · 2020Trial
- Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.Journal of clinical hypertension (Greenwich, Conn.) · 2020Trial
- Effective uric acid-lowering treatment for hypertensive patients with hyperuricemia.Hypertension research : official journal of the Japanese Society of Hypertension · 2017Trial
- Monophosphoryl lipid A boosts macrophage antimicrobial immunity by metabolically regulating source-specific ROS generation.Frontiers in immunology · 2026Article
- Xanthine Oxidoreductase in the Pathogenesis of Endothelial Dysfunction: An Update.Current hypertension reviews · 2024Review
- Xanthine oxidase mediates chronic stress-induced cerebrovascular dysfunction and cognitive impairment.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model.iScience · 2022Article
- Synthesis and biological evaluation of thiazolidine-2-thione derivatives as novel xanthine oxidase inhibitors.PloS one · 2022Article
- Cardio-renal protective effect of the xanthine oxidase inhibitor febuxostat in the 5/6 nephrectomy model with hyperuricemia.Scientific reports · 2020Article
- Effects of uric acid dysregulation on the kidney.American journal of physiology. Renal physiology · 2020Article
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Effect and Mechanism of ShiZhiFang on Uric Acid Metabolism in Hyperuricemic Rats.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy.Oncotarget · 2017Article
- Oxidative Stress and Hypertensive Diseases.The Medical clinics of North America · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 ± 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 ± 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics.
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