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This study aimed to determine how AT\n                      <jats:sub>2<\/jats:sub>\n                      R activation modulates cellular metabolism and to identify pathways relevant to its tissue\u2010protective actions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      3T3\u2010L1 adipocytes, endothelial cells, and renal proximal tubular epithelial cells were treated with the specific AT\n                      <jats:sub>2<\/jats:sub>\n                      R agonist Compound 21 (C21). Targeted liquid chromatography\u2013tandem mass spectrometry was used to quantify amino acids and metabolites involved in energy metabolism and redox homeostasis. Functional analyses included nitrate\/nitrite determination and cystathionine \u03b2\u2010synthase (CBS) activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compound 21 induced shared and cell type\u2010specific metabolic changes. Arginine, citrulline, glucose, and glyceraldehyde 3\u2010phosphate increased consistently across all cell types, whereas citrate decreased. Sulfur\u2010containing metabolites and glutathione\u2010related intermediates increased predominantly in adipocytes and renal cells. Pathway analysis highlighted three metabolic axes affected by C21: arginine biosynthesis, central carbon metabolism, and amino acid\u2010linked redox pathways. Functionally, C21 increased nitrate\/nitrite accumulation in BAECs and CBS activity in RPTECs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Treatment with C21 was associated with a conserved metabolic signature across adipocytes, renal epithelial cells, and endothelial cells involving arginine biosynthesis, central carbon metabolism, and amino acid\u2010linked redox homeostasis. While the response differed among cell types, coordinated changes in arginine, citrulline, glucose, glyceraldehyde 3\u2010phosphate, citrate, and GSH\u2010related metabolites suggest that AT\n                      <jats:sub>2<\/jats:sub>\n                      R signaling is associated with cellular pathways involved in nitric oxide metabolism, energy metabolism, and redox homeostasis. Increased NOx production in BAECs and CBS activity in RPTECs support the cell type\u2010specific metabolic effects of C21.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70314","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:49:08Z","timestamp":1790311748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Metabolomics Reveals a Metabolic Signature Derived From the Stimulation of Cells With the Specific\n                    <scp>\n                      AT\n                      <sub>2<\/sub>\n                      R\n                    <\/scp>\n                    Agonist\n                    <scp>C21<\/scp>"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7437-8987","authenticated-orcid":false,"given":"Jorge Andr\u00e9s","family":"Narv\u00e1ez Pardo","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Faculty of Pharmacy and Biochemistry, Institute of Biological and Physicochemical Chemistry University of Buenos Aires  Buenos Aires Argentina"},{"name":"Department of Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda","family":"Bajicoff","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Faculty of Pharmacy and Biochemistry, Institute of Biological and Physicochemical Chemistry University of Buenos Aires  Buenos Aires Argentina"},{"name":"Department of Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center University of Freiburg  Freiburg 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