{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:51:34Z","timestamp":1793083894002,"version":"4.5.0"},"reference-count":424,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hypertension (HTN) is a major contributor to kidney damage, leading to conditions such as nephrosclerosis and hypertensive nephropathy, significant causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). HTN is also a risk factor for stroke and coronary heart disease. Oxidative stress, inflammation, and activation of the renin\u2013angiotensin\u2013aldosterone system (RAAS) play critical roles in causing kidney injury in HTN. Genetic and environmental factors influence the susceptibility to hypertensive renal damage, with African American populations having a higher tendency due to genetic variants. Managing blood pressure (BP) effectively with treatments targeting RAAS activation, oxidative stress, and inflammation is crucial in preventing renal damage and the progression of HTN-related CKD and ESRD. Interactions between genetic and environmental factors impacting kidney function abnormalities are central to HTN development. Animal studies indicate that genetic factors significantly influence BP regulation. Anti-natriuretic mechanisms can reset the pressure\u2013natriuresis relationship, requiring a higher BP to excrete sodium matched to intake. Activation of intrarenal angiotensin II receptors contributes to sodium retention and high BP. In HTN, the gut microbiome can affect BP by influencing energy metabolism and inflammatory pathways. Animal models, such as the spontaneously hypertensive rat and the chronic angiotensin II infusion model, mirror human essential hypertension and highlight the significance of the kidney in HTN pathogenesis. Overproduction of reactive oxygen species (ROS) plays a crucial role in the development and progression of HTN, impacting renal function and BP regulation. Targeting specific NADPH oxidase (NOX) isoforms to inhibit ROS production and enhance antioxidant mechanisms may improve renal structure and function while lowering blood pressure. Therapies like SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing oxidative stress, inflammation, and RAAS activity, offering renal and antihypertensive protection in managing HTN and CKD. This review emphasizes the critical role of NOX in the development and progression of HTN, focusing on its impact on renal function and BP regulation. Effective BP management and targeting oxidative stress, inflammation, and RAAS activation, is crucial in preventing renal damage and the progression of HTN-related CKD and ESRD.<\/jats:p>","DOI":"10.3390\/antiox13121454","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:18:42Z","timestamp":1732691922000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Oxidative Stress in Kidney Injury and Hypertension"],"prefix":"10.3390","volume":"13","author":[{"given":"Willaim J.","family":"Arendshorst","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4971-8040","authenticated-orcid":false,"given":"Aleksandr E.","family":"Vendrov","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-3493","authenticated-orcid":false,"given":"Nitin","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi K.","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-0908","authenticated-orcid":false,"given":"Nageswara R.","family":"Madamanchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries","volume":"134","author":"Mills","year":"2016","journal-title":"Circulation"},{"key":"ref_2","first-page":"e426","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"138","author":"Whelton","year":"2018","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic Kidney Disease: Challenges, Progress, and Possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin. 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