Salt sensitivity of blood pressure, characterized by blood pressure fluctuations that mirror dietary sodium (Na) intake, is an independent risk factor for cardiovascular morbidity and mortality in people with and without hypertension. We previously found that elevated Na uptake via the amiloride-sensitive epithelial sodium channel (ENaC) in antigen-presenting cells leads to the upregulation of isolevuglandins and proinflammatory cytokines ultimately leading to T cell activation and salt-sensitive hypertension. In addition, we also showed that SMAD3 activation plays a role in inflammation and salt-sensitive hypertension. In previous studies, RGMa has been shown to be upstream of SMAD3. Furthermore, previous studies have also shown that knockdown of RGMa leads to reduced levels of TGFβ1-induced SMAD3 phosphorylation. The exact mechanism by which elevated extracellular Na leads to increased blood pressure remains unknown. We hypothesized that RGMa complexes with TGFβ1R1 to promote SMAD3 phosphorylation ultimately contributing to inflammation in salt-sensitive hypertension. To test our hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na in vitro for 72 hours and subsequently performed bulk RNA sequencing. In additional experiments, we performed an in vivo high Na treatment by utilizing a rigorous salt-loading/depletion protocol on human participants (N = 9) and conducted single-cell transcriptomic analyses. Our bulk RNA sequencing analyses revealed there was no difference in expression of TGFβ1R1 (8837 ± 780.9 vs. 9688 ± 942.5, p =0.350) and TGFβ1R2 (7012 ± 717.0 vs. 7176 ± 633.9, p = 0.059). Interestingly, RGMa (2253 ± 441.0 vs. 516 ± 84.1, p <0.001) and TGFβ1 (5118 ± 353.9 vs. 9067 ± 826.4, p = 0.073) were significantly upregulated in human monocytes after high Na treatment compared to normal salt. However, single-cell transcriptomic analyses found no correlation between the changes in pulse pressure and RGMa (r = 0.5154, p = 0.1911). Our data suggest that RGMa mediates Na-induced inflammation but may not play a role in salt-sensitive hypertension.