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Pathophysiological triggers such as renal ischemia\u2013reperfusion (IR) injury and the accumulation of uremic toxins (UTs), notably indoxyl sulfate (IS), can initiate AKI and affect vascular beds distant from the ischemic site, like the aorta. In this context, purinergic signaling becomes relevant, since its components regulate vascular tone and inflammatory responses. This study aimed to evaluate the impact of AKI induced by IR with or without IS administration on purinergic signaling in the aorta of mice. Renal ischemia was induced by the occlusion of the left renal pedicle for 60 min, followed by reperfusion for 8 days (IR 8) or 15 days (IR 15). Some animals were also treated with saline solution or IS for 15 days. The IR15 group exhibited increased plasma IS concentrations and upregulated adenosine receptor gene expression. Furthermore, in the IR+IS group, there was increased expression of A1, A2a, NTPDase 1, and 2. This shift toward an adenosine-enriched signaling environment may represent a key mechanism linking renal injury to systemic vascular inflammation.<\/jats:p>","DOI":"10.3390\/ijms27146296","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:49:36Z","timestamp":1784184576000},"page":"6296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renal Ischemia\u2013Reperfusion and Uremic Toxins Modulate the Aortic Adenosinergic Axis in Acute Kidney Injury"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1259-5904","authenticated-orcid":false,"given":"Ana Carolina da Costa","family":"Peres","sequence":"first","affiliation":[{"name":"Laboratory of Vascular Biochemistry, Center for Natural and Human Sciences, Federal University of ABC, Santo Andr\u00e9 09280-560, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6272-9238","authenticated-orcid":false,"given":"Jackeline Rodrigues","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biochemistry, Center for Natural and Human Sciences, Federal University of ABC, Santo Andr\u00e9 09280-560, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-8522","authenticated-orcid":false,"given":"Jeferson","family":"Stabile","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biochemistry, Center for Natural and Human Sciences, Federal University of ABC, Santo Andr\u00e9 09280-560, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8219-3421","authenticated-orcid":false,"given":"Carmen Lucia Sanz","family":"Alarta","sequence":"additional","affiliation":[{"name":"Department of Basic Pathology, Biological Sciences Sector, Federal University of Paran\u00e1, Curitiba 81531-980, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-6350","authenticated-orcid":false,"given":"Lia Sumie","family":"Nakao","sequence":"additional","affiliation":[{"name":"Department of Basic Pathology, Biological Sciences Sector, Federal University of Paran\u00e1, Curitiba 81531-980, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-4166","authenticated-orcid":false,"given":"Fernanda Tibolla","family":"Viero","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-3815","authenticated-orcid":false,"given":"Henning","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0855-4791","authenticated-orcid":false,"given":"Cristina Ribas","family":"F\u00fcrstenau","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biochemistry, Center for Natural and Human Sciences, Federal University of ABC, Santo Andr\u00e9 09280-560, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J. 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