ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 62 citations in OpenAlex.
- Antioxidants supplementation in elderly cardiovascular patients.Oxidative medicine and cellular longevity · 2013Trial
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Obesity-Associated Cardiac Fibrosis: Mechanisms and Emerging Therapeutic Targets.Vascular health and risk management · 2026Review
- Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.Journal of cardiovascular translational research · 2025Review
- Glucose Increases Hepatic Mitochondrial Antioxidant Enzyme Activities in Insulin Resistant Rats Following Chronic Angiotensin Receptor Blockade.International journal of molecular sciences · 2022Article
- Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Obesity and sudden cardiac death: Prevalence, pathogenesis, prevention and intervention.Frontiers in cell and developmental biology · 2022Review
- Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities.Advanced drug delivery reviews · 2021Review
- Application of Animal Models in Diabetic Cardiomyopathy.Diabetes & metabolism journal · 2021Review
- Article
- The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection.Antioxidants (Basel, Switzerland) · 2020Review
- Partial Body Mass Recovery After Caloric Restriction Abolishes Improved Glucose Tolerance in Obese, Insulin Resistant Rats.Frontiers in endocrinology · 2020Article
- AMPK: a balancer of the renin-angiotensin system.Bioscience reports · 2019Review
- Angiotensin receptor and tumor necrosis factor-α activation contributes to glucose intolerance independent of systolic blood pressure in obese rats.American journal of physiology. Renal physiology · 2018Article
- Adipose transcriptome analysis provides novel insights into molecular regulation of prolonged fasting in northern elephant seal pups.Physiological genomics · 2018Article
- Angiotensin receptor blockade improves cardiac mitochondrial activity in response to an acute glucose load in obese insulin resistant rats.Redox biology · 2018Article
- Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.The Journal of endocrinology · 2017Article
- The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced obesity in rats.British journal of pharmacology · 2016Article
- Anesthetic Propofol-Induced Gene Expression Changes in Patients Undergoing Coronary Artery Bypass Graft Surgery Based on Dynamical Differential Coexpression Network Analysis.Computational and mathematical methods in medicine · 2016Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of angiotensin receptor type 1 (AT1) contributes to NADPH oxidase (Nox)-derived oxidative stress during metabolic syndrome. However, the specific role of AT1 in modulating redox signaling, mitochondrial function, and oxidative stress in the heart remains more elusive. To test the hypothesis that AT1 activation increases oxidative stress while impairing redox signaling and mitochondrial function in the heart during diet-induced insulin resistance in obese animals, Otsuka Long Evans Tokushima Fatty (OLETF) rats (n = 8/group) were treated with the AT1 blocker (ARB) olmesartan for 6 wk. Cardiac Nox2 protein expression increased 40% in OLETF compared with age-matched, lean, strain-control Long Evans Tokushima Otsuka (LETO) rats, while mRNA and protein expression of the H₂O₂-producing Nox4 increased 40-100%. ARB treatment prevented the increase in Nox2 without altering Nox4. ARB treatment also normalized the increased levels of protein and lipid oxidation (nitrotyrosine, 4-hydroxynonenal) and increased the redox-sensitive transcription factor Nrf2 by 30% and the activity of antioxidant enzymes (SOD, catalase, GPx) by 50-70%. Citrate synthase (CS) and succinate dehydrogenase (SDH) activities decreased 60-70%, whereas cardiac succinate levels decreased 35% in OLETF compared with LETO, suggesting that mitochondrial function in the heart is impaired during obesity-induced insulin resistance. ARB treatment normalized CS and SDH activities, as well as succinate levels, while increasing AMPK and normalizing Akt, suggesting that AT1 activation also impairs cellular metabolism in the diabetic heart. These data suggest that the cardiovascular complications associated with metabolic syndrome may result from AT1 receptor-mediated Nox2 activation leading to impaired redox signaling, mitochondrial activity, and dysregulation of cellular metabolism in the heart.
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