ArticleFrontiers in physiology2015
Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling.
Article in Frontiers in physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial.Scientific reports · 2020Trial
- Finerenone Alleviates Cardiac Microvascular Injury and Neutrophil Extracellular Traps Formation in Diabetic Cardiomyopathy via Regulating AKT1 Phosphorylation.Acta physiologica (Oxford, England) · 2026Article
- Heart failure with a preserved ejection fraction: synergy between cardiac and extracardiac mechanisms and effects of novel therapies.Heart failure reviews · 2026Review
- Article
- Structural and Computational Insights into the Angiotensin II Type 1 Receptor: Advances in Antagonist Design and Implications for Hypertension Therapy (2020-2024).Biomolecules · 2025Review
- Oxidative Stress, Metabolic Impairment and Neuroinflammation are Associated With Target Organ Damage in SHRSP.Physiological research · 2025Article
- The Role of Esaxerenone in the Continuum of Heart Failure With Preserved Ejection Fraction: Insights From a Prospective Observational Study.Clinical cardiology · 2025Observational
- Blocking mineralocorticoid signaling with esaxerenone reduces atherosclerosis in hyperglycemic ApoE KO mice without affecting blood pressure and glycolipid metabolism.Scientific reports · 2025Article
- Effect of esaxerenone on the onset of aortic endothelial dysfunction and circulating microparticles in type 1 diabetic male mice.Scientific reports · 2024Article
- A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice.Journal of atherosclerosis and thrombosis · 2023Article
- ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.American journal of physiology. Heart and circulatory physiology · 2022Article
- Circadian Variation of Blood Pressure in Patients with Chronic Musculoskeletal Pain: A Cross-Sectional Study.International journal of environmental research and public health · 2022Observational
- Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects.Nature reviews. Nephrology · 2022Review
- Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy.International journal of molecular sciences · 2021Article
- Elevated Secretion of Aldosterone Increases TG/HDL-C Ratio and Potentiates The Ox-LDL-Induced Dysfunction of HUVEC.Cell journal · 2021Article
- Aldosterone, Inflammation, Immune System, and Hypertension.American journal of hypertension · 2021Review
- Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation.Handbook of experimental pharmacology · 2021Review
- Oxidative Stress: A Unifying Paradigm in Hypertension.The Canadian journal of cardiology · 2020Review
- Article
- Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress.Life sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepR(db)/LepR(db) (db/db)] mice, a model of DM2, and their counterpart controls [LepR(db)/LepR(+), (db/+) mice] received spironolactone (50 mg/kg body weight/day) or vehicle (ethanol 1%) via oral per gavage for 6 weeks. Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser(1177)) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 and catalase expression, improved sodium nitroprusside and BAY 41-2272-induced relaxation, and increased soluble guanylyl cyclase (sGC) β subunit expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes.
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