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The protective axis of the renin\u2013angiotensin system, consisting of angiotensin-converting enzyme 2 (ACE2)\/angiotensin (Ang)-(1\u20137)\/Mas receptor (MasR), exerts anti-hypertensive and cerebroprotective effects. Thus, we aimed to evaluate whether aging and hypertension may be associated with region-specific changes in the ACE2\/Ang-(1\u20137)\/MasR axis in the brainstem (BS), hypothalamus (Hypot), hippocampus (Hippo), and cerebral cortex (CC) of Wistar rats and spontaneously hypertensive rats (SHRs) at different ages. Ang-(1\u20137) levels were measured by radioimmunoassay, and ACE2 and MasR expression by immunoblotting. In Wistar rats, Ang-(1\u20137) levels decreased with age in all brain areas. At a prehypertensive stage (1\u00a0month of age), SHRs exhibited lower Ang-(1\u20137) levels than Wistar rats in BS, Hypot, Hippo, and CC. In SHRs, Ang-(1\u20137) levels increased at 3 months and subsequently decreased at 12 months in the BS, Hypot, and Hippo, whereas cortical levels declined with age. No differences in Ang-(1\u20137) levels between both strains were found at 3 and 12\u00a0months of age. In line with the reduced hypothalamic Ang-(1\u20137) levels, MasR and ACE2 protein abundance were also decreased in the Hypot of 1-month-old SHRs compared with age-matched Wistar rats. In contrast, MasR expression was higher in BS of 1-month-old SHRs compared with age-matched Wistar rats, suggesting a compensatory response. At 1\u00a0month of age, ACE2 and MasR protein levels did not differ between strains in the Hippo or CC. We conclude that abnormal changes in the expression of the brain ACE2\/Ang-(1\u20137)\/MasR axis early in life may predispose to the development of hypertension with age.<\/jats:p>","DOI":"10.1042\/cs20261834","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:08:35Z","timestamp":1789387715000},"page":"2307-2320","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-related alterations in the brain ACE2\/Ang-(1\u20137)\/Mas receptor axis in normotensive and spontaneously hypertensive rats"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-1129","authenticated-orcid":false,"given":"Natalia\u00a0L.","family":"Rukavina Mikusic","sequence":"first","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9994-9068","authenticated-orcid":false,"given":"Ornella","family":"Conte","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-6935","authenticated-orcid":false,"given":"Ezequiel","family":"Bruna-Haupt","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica\u00a0M.","family":"Pineda Payares","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda\u00a0F.","family":"Sirri","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-4733","authenticated-orcid":false,"given":"Myriam","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"2Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de F\u00edsico-Matem\u00e1ticas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-5406","authenticated-orcid":false,"given":"Lisete\u00a0C.","family":"Michelini","sequence":"additional","affiliation":[{"name":"3University of S\u00e3o Paulo, Department of Physiology and Biophysics, Institute of Biomedical Sciences, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4351-0057","authenticated-orcid":false,"given":"Fernando\u00a0P.","family":"Dominici","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1887-7367","authenticated-orcid":false,"given":"Pablo","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"4Department of Physiology, Neuroscience Research Center, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-0388","authenticated-orcid":false,"given":"Mariela\u00a0M.","family":"Gironacci","sequence":"additional","affiliation":[{"name":"1Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Qu\u00edmica Biol\u00f3gica and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2026100803411835600_B1","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","article-title":"Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology","volume":"98","author":"Forrester","year":"2018","journal-title":"Physiol. 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