ArticleHypertension (Dallas, Tex. : 1979)2016
Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.
Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 100 citations in OpenAlex.
- Sex Differences and Oxidative Stress in Cardiovascular Disease.Physiology (Bethesda, Md.) · 2026Review
- Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease: From Molecular Mechanisms to Biomarkers and Targeted Therapies.Antioxidants (Basel, Switzerland) · 2026Review
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Butyrate mitigates multi-organ damage in urosepsis: associated changes in the renal NOX4/ROS/NF-κB axis and gut microbiota.Frontiers in cellular and infection microbiology · 2026Article
- Mild Hyperuricemia Attenuates Salt-Sensitive Hypertension and Kidney Damage.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Genetic and Pharmacological Inhibition of NOX4 Protects Against Rhabdomyolysis-Induced Acute Kidney Injury Through Suppression of Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Mechanical Stress Induced NOX2 Promotes Endothelial Dysfunction in Ventilator-Induced Lung Injury: Potential Treatment with Quercetin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oxidative Stress in Renal Health.Antioxidants (Basel, Switzerland) · 2025Article
- Delineating the NOX-Mediated Promising Therapeutic Strategies for the Management of Various Cardiovascular Disorders: A Comprehensive Review.Current vascular pharmacology · 2025Review
- Renal Medulla in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- Optical Imaging Demonstrates Tissue-Specific Metabolic Perturbations in Mblac1 Knockout Mice.IEEE journal of translational engineering in health and medicine · 2024Article
- Effects of ROS pathway inhibitors and NADH and FADHArchives of biochemistry and biophysics · 2023Article
- Redox regulation in diabetic kidney disease.American journal of physiology. Renal physiology · 2023Review
- Redox Signaling in Chronic Kidney Disease-Associated Cachexia.Antioxidants (Basel, Switzerland) · 2023Review
- Reactivity of renal and mesenteric resistance vessels to angiotensin II is mediated by NOXA1/NOX1 and superoxide signaling.American journal of physiology. Renal physiology · 2023Article
- Oxidative Stress, Antioxidants and Hypertension.Antioxidants (Basel, Switzerland) · 2023Review
- NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation.Theranostics · 2023Article
- Epigenetics of the blood pressure reactivity to salt: Is the salt sensitive phenotype correctable?BioImpacts : BI · 2023Article
- Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model.iScience · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the ≈68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134±5 versus 151±3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (P<0.05) in SS(Nox4-/-) compared with SS rats in the renal cortex. Thus, the mutation of Nox4 seems to modify transcription of several genes in ways that contribute to the protective effects observed in the SS(Nox4-/-) rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.