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At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague\u2013Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus enhances sympathetic tone and contributes to age-dependent hypertension, (2) age-dependent hypertension is associated with cognitive impairment, and (3) lowering blood pressure in aged rats with established hypertension improves cognitive function. We found male, but not female, rats develop age-dependent hypertension with enhanced sympathetic tone, BBB disruption, and neuroinflammation in the PVN. Aged hypertensive male rats also showed impairments in recognition and spatial memory. Utilizing pharmacological interventions, blood pressure was lowered in male rats with established hypertension using either losartan (LOS) or hydrochlorothiazide. However, only losartan improved recognition memory. Further, LOS reduced BBB disruption, microglial activation, astrocyte reactivity, and proinflammatory cytokine expression in the PVN which we speculate contributes to a decrease in blood pressure. These data show SD rats develop age-dependent hypertension and cognitive impairment in a sex-dependent manner. However, not all antihypertensive agents improve cognitive function equally as only losartan, an angiotensin II type 1 receptor antagonist (AT1R) improved recognition memory. Thus, AT1R antagonists represent a potential therapeutic approach for treating cognitive decline in the aging population.<\/jats:p>","DOI":"10.1007\/s11357-024-01409-4","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T18:37:04Z","timestamp":1733251024000},"page":"3007-3026","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague\u2013dawley rat"],"prefix":"10.1007","volume":"47","author":[{"given":"Kayla M.","family":"Nist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Bard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brannon","family":"McBride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Capriglione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse D.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Farb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-5618","authenticated-orcid":false,"given":"Richard D.","family":"Wainford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"issue":"6","key":"1409_CR1","first-page":"e13","volume":"71","author":"PK Whelton","year":"2018","unstructured":"Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC, Spencer CC, et al. 2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. 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