Interplay of renal, vascular, and immune signaling in salt sensitivity of blood pressure: AP-1 as an emerging therapeutic target

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.