ArticleThe Journal of clinical investigation2011
Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.
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Who cites it
137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Renal effects and safety between Asian and non-Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists.Journal of diabetes · 2024Pooled it
- Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.Journal of human hypertension · 2016Pooled it
- Aldosterone Synthase Inhibitors: Emerging Therapeutic Strategies in Resistant Hypertension.Life (Basel, Switzerland) · 2026Review
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- The non-steroidal mineralocorticoid receptor blocker esaxerenone reduces glomerular hyperfiltration and albuminuria.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Aldosterone-mineralocorticoid receptor interactions: new insights and therapeutic perspectives in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Cardioprotective Effects of Finerenone Associated With the Suppression of Myocardial Sodium Accumulation in Aldosterone/Salt-Loaded Rats.Journal of the American Heart Association · 2026Article
- Rho/ROCK Signaling Pathway in Kidney Diseases: Mechanisms and Therapeutic Perspectives.Biomedicines · 2026Review
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Finerenone as an add-on treatment to conventional therapies for the patients with diabetic kidney disease.BMC nephrology · 2026Article
- Review
- Probenecid protects against contrast-induced nephropathy through modulation of small Rho GTPases and Pannexin1 channels in Wistar rats.Clinical and experimental nephrology · 2025Article
- Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.Kidney360 · 2025Review
- From pathophysiology to novel approaches for obesity-associated hypertension.Clinical kidney journal · 2025Review
- Rac1 Suppression by the Focal Adhesion Protein GIT ArfGAP2 and Podocyte Protection.Journal of the American Society of Nephrology : JASN · 2025Article
- Single-Cell Analysis of Endothelial Cell Injury in IgA Nephropathy.Immunity, inflammation and disease · 2025Article
- Article
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- Early reduction of skin potassium without sodium accumulation in the pathogenesis of salt sensitivity in primary aldosteronism.Frontiers in pharmacology · 2025Article
- Circulating RAC1 contributed to steroid-sensitive nephrotic syndrome: Mendelian randomization, single-cell RNA-sequencing, proteomic, and experimental evidence.Renal failure · 2024Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), a nuclear transcription factor regulated by the steroid aldosterone, and the small GTPase Rac1, which is implicated in proteinuric kidney disease. We here show that high-salt loading activates Rac1 in the kidneys in rodent models of salt-sensitive hypertension, leading to blood pressure elevation and renal injury via an MR-dependent pathway. We found that a high-salt diet caused renal Rac1 upregulation in salt-sensitive Dahl (Dahl-S) rats and downregulation in salt-insensitive Dahl (Dahl-R) rats. Despite a reduction of serum aldosterone levels, salt-loaded Dahl-S rats showed increased MR signaling in the kidneys, and Rac1 inhibition prevented hypertension and renal damage with MR repression. We further demonstrated in aldosterone-infused rats as well as adrenalectomized Dahl-S rats with aldosterone supplementation that salt-induced Rac1 and aldosterone acted interdependently to cause MR overactivity and hypertension. Finally, we confirmed the key role of Rac1 in modulating salt susceptibility in mice lacking Rho GDP-dissociation inhibitor α. Therefore, our data identify Rac1 as a determinant of salt sensitivity and provide insights into the mechanism of salt-induced hypertension and kidney injury.
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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.