Interplay of Renal, Vascular, and Immune Signaling in Salt Sensitivity of Blood Pressure: AP-1 as an Emerging Therapeutic Target
6 affiliations
- 1Department of Medicine, Division of Genetic Medicine and Clinical Pharmacology, Vanderbilt Health, Nashville, TN, 37212, USA.
- 2Department of Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha, Punjab, 40100, Pakistan.
- 3Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37212, USA
- 4Vanderbilt Institute for Global Health, Vanderbilt Health, Nashville, TN, 37212, United States.
- 5Vanderbilt Center for Immunobiology, Vanderbilt Health, Nashville, TN, 37212, United States
- 6Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt Health, Nashville, TN, 37212, United States
Abstract
Some individuals develop elevated blood pressure in response to increased dietary sodium intake, a phenotype known as salt sensitivity of blood pressure (SSBP). Our understanding of SSBP has expanded beyond the traditional view of sodium overload and fluid retention to recognize it as a complex immunoinflammatory process that contributes to progressive damage across multiple organs, particularly the kidneys and vasculature. High-salt exposure can activate immune cells, leading to increased production of reactive oxygen species (ROS), reduced nitric oxide (NO) bioavailability, and the release of proinflammatory cytokines. This persistent low-grade inflammation disrupts renal and vascular homeostasis and further exacerbates immune dysregulation. Growing evidence suggests that dysregulation of key transcriptional regulators, including hypoxia-inducible factor-1α (HIF-1α), mineralocorticoid receptor (MR), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1), may play an important role in the development of SSBP by modulating immune activation, renal sodium handling, vascular dysfunction, and inflammatory signaling pathways. This review provides an overview of the current understanding of renal, vascular, and immune cell cross-talk in SSBP and highlights the emerging role of AP-1 as an important mechanistic regulator and potential therapeutic target.
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BibTeX
@article{ahmad2026interplay,
title = {{Interplay of Renal, Vascular, and Immune Signaling in Salt Sensitivity of Blood Pressure: AP-1 as an Emerging Therapeutic Target}},
author = {Taseer Ahmad and Ali Raza and Rabeea Ameer and Mohammad Saleem and Mohd Mabood Khan and Annet Kirabo},
journal = {American journal of physiology. Heart and circulatory physiology},
year = {2026},
month = oct,
doi = {10.1152/ajpheart.90175.2026},
url = {https://doi.org/10.1152/ajpheart.90175.2026},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Interplay of Renal, Vascular, and Immune Signaling in Salt Sensitivity of Blood Pressure: AP-1 as an Emerging Therapeutic Target
AU - Taseer Ahmad
AU - Ali Raza
AU - Rabeea Ameer
AU - Mohammad Saleem
AU - Mohd Mabood Khan
AU - Annet Kirabo
PY - 2026
DA - 2026/10/07
JO - American journal of physiology. Heart and circulatory physiology
DO - 10.1152/ajpheart.90175.2026
UR - https://doi.org/10.1152/ajpheart.90175.2026
AB - Some individuals develop elevated blood pressure in response to increased dietary sodium intake, a phenotype known as salt sensitivity of blood pressure (SSBP). Our understanding of SSBP has expanded beyond the traditional view of sodium overload and fluid retention to recognize it as a complex immunoinflammatory process that contributes to progressive damage across multiple organs, particularly the kidneys and vasculature. High-salt exposure can activate immune cells, leading to increased production of reactive oxygen species (ROS), reduced nitric oxide (NO) bioavailability, and the release of proinflammatory cytokines. This persistent low-grade inflammation disrupts renal and vascular homeostasis and further exacerbates immune dysregulation. Growing evidence suggests that dysregulation of key transcriptional regulators, including hypoxia-inducible factor-1α (HIF-1α), mineralocorticoid receptor (MR), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1), may play an important role in the development of SSBP by modulating immune activation, renal sodium handling, vascular dysfunction, and inflammatory signaling pathways. This review provides an overview of the current understanding of renal, vascular, and immune cell cross-talk in SSBP and highlights the emerging role of AP-1 as an important mechanistic regulator and potential therapeutic target.
SN - 0363-6135
SN - 1522-1539
ER -