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In this study, we analyzed cerebrospinal fluid (CSF) samples from spontaneously hypertensive rats (SHR) that had been treated with either amlodipine or atenolol for one year and compared these to normotensive Wistar Kyoto rats (WKY). Mass spectrometry-based proteomic analysis of the CSF samples was conducted to identify both the impact of hypertension as well as antihypertensive treatment on CSF proteomics. Both systolic and diastolic blood pressure were increased in hypertensive rats, and both medications lowered blood pressure compared to untreated SHR rats. The analysis of the CSF proteome revealed that hypertension resulted in alterations to processes associated with the development of the central nervous system, inflammation and blood coagulation. The latter included proteins such as YKL-40, KNG1, DAG1, and members of the Serpin family. Amlodipine treatment resulted in changes to proteins involved in gas transport (including CA2, HBB, and HBA1), whereas atenolol treatment led to changes in the complement and coagulation cascade (including CFH, KNG1, APOE, and AHSG). A comparison of the two antihypertensive treatments revealed alterations in pathways associated with cell adhesion, central nervous system development, and vascular development. These findings show that hypertension and long-term treatment with antihypertensive medications elicit distinct effects on the CSF proteome.<\/jats:p>","DOI":"10.1038\/s41598-025-21450-3","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:47:39Z","timestamp":1761662859000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebrospinal fluid proteomic analysis of long-term antihypertensive treatment with amlodipine and atenolol in hypertensive rats"],"prefix":"10.1038","volume":"15","author":[{"given":"Nina G.","family":"Smets","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty M.","family":"Tijms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"de Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander R.","family":"Piersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thang V.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie R.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik N. 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