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The presence of RAS components throughout the nephron has been widely discussed. The (pro)renin receptor (PRR) is a member of the RAS widely expressed in the body of humans and rodents. In the kidney, PRR is expressed in mesangial cells, renal vasculature, and tubules of the proximal and distal nephron. Binding of the PRR to renin and prorenin promotes angiotensin (Ang) I-mediated sodium (Na+) reabsorption via the epithelial sodium channel (ENaC). The Goldblatt 2-kidney 1-clip (2K1C) is a model of experimental renovascular hypertension that displays activation of systemic and intrarenal RAS. We use the 2K1C hypertension mouse model for 7 days to evaluate the role of the PRR on renal \u03b1ENaC expression, Na+ reabsorption, and BP using pharmacological systemic blockade of the PRR with PRO20 peptide. Mice undergoing or not to 2K1C surgery (0.13 mm clip internal gap) were chronically infused with PRO20 and compared to sham (control) mice to assess changes in systolic BP (SBP) and diastolic BP (DBP), intrarenal angiotensin-converting enzyme (ACE) activity, Ang II, and renal \u03b1ENaC expression and natriuretic responses after a saline challenge. Renal artery obstruction increased SBP and DBP, intrarenal ACE activity, Ang II levels, Na+ retention, and \u03b1ENaC expression in both kidneys. PRO20 prevented the increases in SBP, DBP, attenuated Na+ retention, and blunted intrarenal Ang II and \u03b1ENaC levels in non-clipped kidneys of 2K1C mice. Chronic infusion of the PRR for 7 days prevents hypertensive responses in part due to impaired \u03b1ENaC upregulation and intrarenal Ang II formation in the early phase of the development of renovascular hypertension in 2K1C Goldblatt mice.<\/jats:p>","DOI":"10.3390\/ijms26094177","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:48:33Z","timestamp":1745840913000},"page":"4177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["(Pro)renin Receptor Blockade Prevents Increases in Systolic Blood Pressure, Sodium Retention, and \u03b1ENaC Protein Expression in the Kidney of 2K1C Goldblatt Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Pilar","family":"C\u00e1rdenas","sequence":"first","affiliation":[{"name":"Instituto de Qu\u00edmica, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Cid-Salinas","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison C.","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Castillo-Geraldo","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-6979","authenticated-orcid":false,"given":"Lilian Caroline Gon\u00e7alves","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Disciplina de Nefrologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Yokota","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Disciplina de Nefrologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9776-3298","authenticated-orcid":false,"given":"Zoe","family":"Vallotton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulce Elena","family":"Casarini","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Disciplina de Nefrologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minolfa C.","family":"Prieto","sequence":"additional","affiliation":[{"name":"Department of Physiology and Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n A.","family":"Lorca","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-1448","authenticated-orcid":false,"given":"Alexis A.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","unstructured":"Fountain, J.H., and Lappin, S.L. 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