ArticleHypertension (Dallas, Tex. : 1979)2012
Tumor necrosis factor α decreases nitric oxide synthase type 3 expression primarily via Rho/Rho kinase in the thick ascending limb.
Article in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Direct pharmacological targeting of RAC1 by chlorogenic acid: A novel therapeutic approach for mesangial proliferative glomerulonephritis.Acta pharmaceutica Sinica. B · 2026Article
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- Augmentation of Nitric Oxide Deficient Hypertension by High Salt Diet Is Associated With Reduced TNF-α Receptor Type 1 Expression in the Kidneys.American journal of hypertension · 2024Article
- Responses to Ang II (Angiotensin II), Salt Intake, and Lipopolysaccharide Reveal the Diverse Actions of TNF-α (Tumor Necrosis Factor-α) on Blood Pressure and Renal Function.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets.Frontiers in immunology · 2022Review
- Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice.BioMed research international · 2020Article
- New Insights on the Role of Sodium in the Physiological Regulation of Blood Pressure and Development of Hypertension.Frontiers in cardiovascular medicine · 2019Article
- Inflammation in Salt-Sensitive Hypertension and Renal Damage.Current hypertension reports · 2018Review
- Renal effects of cytokines in hypertension.Current opinion in nephrology and hypertension · 2018Review
- Salt, Hypertension, and Immunity.Annual review of physiology · 2018Review
- Inflammatory cytokines regulate renal sodium transporters: how, where, and why?American journal of physiology. Renal physiology · 2017Review
- Hydrogen sulfide alleviates hypertensive kidney dysfunction through an epigenetic mechanism.American journal of physiology. Heart and circulatory physiology · 2017Article
- Targeting cytokine signaling in salt-sensitive hypertension.American journal of physiology. Renal physiology · 2016Review
- Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs.American journal of physiology. Renal physiology · 2016Article
- Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.Cell metabolism · 2016Article
- Posttranscriptional and transcriptional regulation of endothelial nitric-oxide synthase during hypoxia: the role of microRNAs.Cellular & molecular biology letters · 2016Review
- Inflammation, immunity, and hypertensive end-organ damage.Circulation research · 2015Review
- Dual regulation of tumor necrosis factor-α on myosin light chain phosphorylation in vascular smooth muscle.American journal of physiology. Heart and circulatory physiology · 2015Article
- Angiotensin II-induced hypertension blunts thick ascending limb NO production by reducing NO synthase 3 expression and enhancing threonine 495 phosphorylation.American journal of physiology. Renal physiology · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inappropriate Na(+) reabsorption by thick ascending limbs (THALs) induces hypertension. NO produced by NO synthase type 3 (NOS3) inhibits NaCl reabsorption by THALs. Tumor necrosis factor α (TNF-α) decreases NOS3 expression in endothelial cells and contributes to increases in blood pressure. However, the effects of TNF-α on THAL NOS3 and the signaling cascade are unknown. TNF-α activates several signaling pathways, including Rho/Rho kinase (ROCK), which is known to reduce NOS3 expression in endothelial cells. Therefore, we hypothesized that TNF-α decreases NOS3 expression via Rho/ROCK in rat THAL primary cultures. THAL cells were incubated with either vehicle or 1 nmol/L of TNF-α for 24 hours, and NOS3 expression was measured by Western blot. TNF-α decreased NOS3 expression by 51 ± 6% (P<0.002) and blunted stimulus-induced NO production. A 10-minute treatment with TNF-α stimulated RhoA activity by 60 ± 23% (P<0.04). Inhibition of Rho GTPase with 0.05 μg/mL of C3 exoenzyme blocked TNF-α-induced reductions in NOS3 expression by 30 ± 8% (P<0.02). Inhibition of ROCK with 10 μmol/L of H-1152 blocked TNF-α-induced decreases in NOS3 expression by 66 ± 15% (P<0.001). Simultaneous inhibition of Rho and ROCK had no additive effect. Myosin light chain kinase, NO, protein kinase C, mitogen-activated kinase kinase, c-Jun amino terminal kinases, and Rac-1 were also not involved in TNF-α-induced decreases in NOS3 expression. We conclude that TNF-α decreases NOS3 expression primarily via Rho/ROCK in rat THALs. These data suggest that some of the beneficial effects of ROCK inhibitors in hypertension could be attributed to the mitigation of TNF-α-induced reduction in NOS3 expression.
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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.