ArticleJournal of the American Society of Nephrology : JASN2012
Angiotensin II- and salt-induced kidney injury through Rac1-mediated mineralocorticoid receptor activation.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 100 citations in OpenAlex.
- Effects of a Hypertension Management Mobile App on Urinary Sodium Excretion in Patients With Chronic Kidney Disease: Randomized Controlled Trial.JMIR mHealth and uHealth · 2026Trial
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Research Progress on the ARHGEF Family in Cardiovascular Diseases.Cell biochemistry and function · 2026Review
- Pendrin is upregulated by corticosterone and participates in its pressor response.American journal of physiology. Renal physiology · 2026Article
- Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.Kidney360 · 2025Review
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- Rac1 Suppression by the Focal Adhesion Protein GIT ArfGAP2 and Podocyte Protection.Journal of the American Society of Nephrology : JASN · 2025Article
- Semaglutide and adenosine alleviate obesity-induced kidney injury, with observed modulation of the Txnip/NLRP3 pathway.Diabetology & metabolic syndrome · 2025Article
- Angiotensin II acts through Rac1 to upregulate pendrin: role of NADPH oxidase.American journal of physiology. Renal physiology · 2024Article
- Review
- Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice.International journal of molecular sciences · 2023Article
- Rac1 inhibition protects the kidney against kidney ischemia/reperfusion through the inhibition of macrophage migration.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Review
- Overview of the safety, efficiency, and potential mechanisms of finerenone for diabetic kidney diseases.Frontiers in endocrinology · 2023Review
- Mineralocorticoid Receptor-Associated Mechanisms in Diabetic Kidney Disease and Clinical Significance of Mineralocorticoid Receptor Antagonists.American journal of nephrology · 2023Review
- Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.International journal of molecular sciences · 2022Review
- The Time to Reconsider Mineralocorticoid Receptor Blocking Strategy: Arrival of Nonsteroidal Mineralocorticoid Receptor Blockers.Current hypertension reports · 2022Review
- Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells.Scientific reports · 2022Article
- Identifying the molecular mechanisms of sepsis-associated acute kidney injury and predicting potential drugs.Frontiers in genetics · 2022Article
- Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β1 pathway in mice induced with aldosterone.Frontiers in immunology · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to renal impairment through Rac1-mediated activation of the MR, but whether angiotensin II also promotes renal injury through this mechanism is unknown. Here, we placed angiotensin II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks and treated some animals with adrenalectomy, the MR antagonist eplerenone, the Rac inhibitor EHT1864, or hydralazine. High-salt intake, but not low-salt intake, led to hypertension and prominent kidney injury. Adrenalectomy prevented angiotensin II/salt-induced nephropathy in mice receiving high-salt intake, which was recapitulated by aldosterone supplementation, suggesting the involvement of aldosterone/MR signaling. Plasma aldosterone levels, however, were lower in high- than low-salt conditions. Instead, angiotensin II/salt-evoked MR activation associated with Rac1 activation and was not dependent on plasma aldosterone level. Both EHT1864 and eplerenone repressed the augmented MR signaling and mitigated kidney injury with partial but significant reduction in BP with high-salt intake. Hydralazine similarly reduced BP, but it neither suppressed the Rac1-MR pathway nor ameliorated the nephropathy. Taken together, these results show that angiotensin II and salt accelerate kidney injury through Rac1-mediated MR activation. Rac inhibition may be a promising strategy for the treatment of CKD.
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