ArticleIranian journal of pharmaceutical research : IJPR2011
Spironolactone inhibits NADPH oxidase-induced oxidative stress and enhances eNOS in human endothelial cells.
Article in Iranian journal of pharmaceutical research : IJPR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Impact of mineralocorticoid receptor antagonist in renal transplant patients: a systematic review and meta-analysis of randomized controlled trials.Journal of nephrology · 2020Pooled it
- Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.Experimental gerontology · 2016Trial
- Molecular Mechanisms and Clinical Evidence Supporting the Four Pillars of Therapy in Diabetic Kidney Disease: Emerging Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Oxidative Stress Biomarkers in Hypertension.Current medicinal chemistry · 2025Review
- Clinical Properties and Non-Clinical Testing of Mineralocorticoid Receptor Antagonists in In Vitro Cell Models.International journal of molecular sciences · 2024Review
- A Systematic Review on Advances in Management of Oxidative Stress-Associated Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.International journal of molecular sciences · 2023Review
- Nonepithelial mineralocorticoid receptor activation as a determinant of kidney disease.Kidney international supplements · 2022Review
- The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.Kidney international supplements · 2022Review
- Parenteral Nutrition and Cardiotoxicity.Cardiovascular toxicology · 2021Review
- COVID-19-The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection.Pharmaceuticals (Basel, Switzerland) · 2021Review
- SRC-3 Knockout Attenuates Myocardial Injury Induced by Chronic Intermittent Hypoxia in Mice.Oxidative medicine and cellular longevity · 2021Article
- Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism.Frontiers in cardiovascular medicine · 2021Review
- Spironolactone ameliorates endothelial dysfunction through inhibition of the AGE/RAGE axis in a chronic renal failure rat model.BMC nephrology · 2019Article
- Cellular death, reactive oxygen species (ROS) and diabetic complications.Cell death & disease · 2018Review
- Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.Journal of diabetes research · 2018Article
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates that aldosterone plays a critical role in the mediation of oxidative stress and vascular damage. NADPH oxidase has been recognized as a major source of oxidative stress in vasculature. However, the relation between NADPH oxidase in aldosterone-mediated oxidative stress in endothelial cells remains to be ascertained. The present study aimed to investigate the relevant role of NADPH oxidase in aldosterone induced oxidative stress and the functional consequence of this effect on endothelial function. Additionally, we attempted to examine the potential role of the mineralocorticoid receptor (MR) antagonist; spironolactone (spiro) in this scenario. Human umbilical artery endothelial cells (HUAECs) were incubated with aldosterone (100 nmol/L, 24 h) in the absence and presence of Spiro (1 µmol/L). The results showed that aldosterone significantly increased the protein expression of NADPH oxidase subunits (Nox2, p47(phox) and p22(phox)) and that spiro markedly inhibited these changes. Functionally, this was associated with an elevation in NADPH oxidase activity and 3-nitrotyrosine (3-NT) as a biochemical marker of oxidative stress. However, pre-incubation with spiro inhibited these consequences. Moreover, MR protein expression was upregulated by aldosterone whereas this effect was suppressed by Spiro. While aldosterone effectively inhibited endothelial nitric oxide (eNOS) protein expression, pretreatment with spiro markedly restored it to its normal level. In conclusion, the results achieved suggest that aldosterone may play a critical role in NADPH oxidase-mediated oxidative stress resulting in reduced eNOS expression in human endothelial cells. Spiro effectively reversed these consequences, suggesting its potential vasculoprotective effect in endothelial dysfunction.
Indexed as
Identifiers
24250362PMC3828907W2301657327What OpenQuestion holds
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.