ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2013
Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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124 citing papers in PubMed, 177 citations in OpenAlex.
- Review
- Human plasma metabolomics reveals metabolic targets for intervention in salt-sensitive hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- HMGB1 drives T-cell activation in hypertensive males and females.American journal of physiology. Renal physiology · 2025Article
- Differential composition of lymphocyte subpopulations and activation between the hypertensive Bph/2 and normotensive Bpn/3 mouse strains.Frontiers in immunology · 2025Article
- Profile of circulating lymphocyte subsets in patients with atrial fibrillation: implications for the comorbidity of hypertension.Archives of medical science : AMS · 2025Article
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- Immune Mechanisms in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure.Current hypertension reports · 2024Review
- Immune and inflammatory mechanisms in hypertension.Nature reviews. Cardiology · 2024Review
- Article
- Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- A new immune disease: systemic hypertension.Clinical kidney journal · 2023Review
- Chronic treatment with IL-25 increases renal M2 macrophages and reduces renal injury in obese Dahl salt-sensitive rats during the prepubescent stage.American journal of physiology. Renal physiology · 2023Article
- Renal histaminergic system and acute effects of histamine receptor 2 blockade on renal damage in the Dahl salt-sensitive rat.American journal of physiology. Renal physiology · 2023Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- The link between immunity and hypertension in the kidney and heart.Frontiers in cardiovascular medicine · 2023Review
- Deeper insight into the role of IL-17 in the relationship beween hypertension and intestinal physiology.Journal of inflammation (London, England) · 2022Review
- Genetic Modifications to Alter Blood Pressure Level.Biomedicines · 2022Review
- Article
- Innate immunity and clinical hypertension.Journal of human hypertension · 2022Review
64 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
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Abstract
Hypertension and renal damage in Dahl SS rats are associated with increased infiltrating immune cells in the kidney. To examine the role of infiltrating immune cells in this disease process, a zinc finger nuclease targeting bases 672-706 of recombination-activating gene 1 (Rag1) was injected into the pronucleus of Dahl SS (SS/JrHsdMcwi) strain embryos and implanted in pseudopregnant females. This strategy yielded a rat strain with a 13-base frame-shift mutation in the target region of Rag1 and a deletion of immunoreactive Rag1 protein in the thymus. Flow cytometry demonstrated that the Rag1-null mutant rats have a significant reduction in T and B lymphocytes in the circulation and spleen. Studies were performed on SS and Rag1-null rats fed a 4.0% NaCl diet for 3 wk. The infiltration of T cells into the kidney following high-salt intake was significantly blunted in the Rag1-null rats (1.7 ± 0.6 × 10(5) cells/kidney) compared with the Dahl SS (5.6 ± 0.9 × 10(5) cells/kidney). Accompanying the reduction in infiltration of immune cells in the kidney, mean arterial blood pressure and urinary albumin excretion rate were significantly lower in Rag1-null mutants (158 ± 3 mmHg and 60 ± 16 mg/day, respectively) than in SS rats (180 ± 11 mmHg and 251 ± 37 mg/day). Finally, a histological analysis revealed that the glomerular and tubular damage in the kidneys of the SS rats fed a high-salt diet was also attenuated in the Rag1 mutants. These studies demonstrate the importance of renal infiltration of immune cells in the pathogenesis of hypertension and renal damage in Dahl SS rats.
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