ArticleThe Journal of biological chemistry2009
Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 102 citations in OpenAlex.
- Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.American journal of physiology. Heart and circulatory physiology · 2016Trial
- The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism.Journal of clinical medicine · 2023Article
- A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice.Journal of atherosclerosis and thrombosis · 2023Article
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- 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
- Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS-CoV-2 infection.Pulmonary circulation · 2022Article
- Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease.International journal of molecular sciences · 2022Review
- Network medicine in Cardiovascular Research.Cardiovascular research · 2021Review
- Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging.Frontiers in molecular biosciences · 2021Review
- Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease.Journal of veterinary pharmacology and therapeutics · 2020Review
- Study of the Differentially Expressed Genes in theMetabolites · 2019Article
- Systems Biology Approaches to Redox Metabolism in Stress and Disease States.Antioxidants & redox signaling · 2018Review
- NEDD9 targetsScience translational medicine · 2018Article
- The Renin-Angiotensin-Aldosterone System as a Therapeutic Target in Late Injury Caused by Ischemia-Reperfusion.International journal of endocrinology · 2018Review
- Guanylyl cyclase sensitivity to nitric oxide is protected by a thiol oxidation-driven interaction with thioredoxin-1.The Journal of biological chemistry · 2017Article
- Responses to reductive stress in the cardiovascular system.Free radical biology & medicine · 2017Review
- The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor.Antioxidants & redox signaling · 2017Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO(.)); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO(.) to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10(-9)-10(-7) mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a beta(1)-subunit cysteinyl residue demonstrated previously to modulate NO(.) sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC beta(1)-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H(2)O(2)) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H(2)O(2) did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO(.)-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC.
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Registered trials
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