Sulfonated peptide alleviates hypertensive renal injury via antioxidant, anti-inflammatory, and renal metabolomics.

Excessive dietary salt intake is a well-established risk factor for hypertension, with numerous underscoring its significant role in the pathogenesis of cardiovascular diseases. Dietary management is widely recognized as essential for both the prevention and treatment of hypertension. This study aimed to evaluate the preventive efficacy of a sulfonated peptide, Leucyl-glycyl-asparaginyl-glycyl-cysteinylsulfonic acid-proline (Leu-Gly-Asn-Gly-Cya-Pro, SLP), against high-salt-induced hypertension and renal injury, thereby providing new insights into hypertension prevention strategies. Compared with the unsulfonated peptide, Leucyl-glycyl- asparaginyl-glycyl-cysteinyl-proline (Leu-Gly-Asn-Gly-Cys-Pro, LP), SLP was more effective in attenuating the elevation of blood pressure, inhibiting renal fibrosis, improving markers of renal injury (alpha-1-microglobulin and uric acid), and reducing levels of inflammatory factors and adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-1β). Additionally, SLP upregulated endothelial nitric oxide synthase while downregulating inducible nitric oxide synthase in the kidney. Similarly, high levels of nuclear factor-kappa B and phosphorylated nuclear factor-kappa B induced by high-salt in the kidney were effectively prevented by SLP treatment. Furthermore, SLP exerted antihypertensive effects through the regulation of tryptophan, purine, glycerophospholipid, and cysteine metabolism, as well as the citrate cycle. Overall, sulfonation modification enhances the anti-inflammatory and metabolic regulatory activities of peptides, with the sulfonated peptides SLP significantly preventing high-salt-induced hypertension and its associated renal complications.