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However, its impact on uterine immune cell populations remains unclear. We hypothesized that SSHTN alters immune cell homeostasis, induces inflammation, and promotes lymphangiogenesis in the uterus, and that these effects can be mitigated by pharmacological blood pressure (BP) reduction and anti-inflammatory macrophage augmentation. To test the hypothesis, female C57BL6\/J mice were given nitro-L-arginine methyl ester hydrochloride (0.5 mg\/ml) in drinking water for 2 weeks, followed by a 2-week washout period. Mice were then subjected to a 4% high-salt diet (SSHTN) for 3 weeks. Another group of mice received either hydralazine (HYD; 250 mg\/l in drinking water), a vasodilator (SSHTN+HYD), or AVE0991 (AVE; 0.58 \u00b5mol\/kg body weight\/day), a nonpeptide Mas receptor agonist, through daily intraperitoneal injections (SSHTN+AVE). Control mice received tap water and a standard diet for the entire treatment period. Flow cytometry data revealed a significant decrease in total uterine CD45+ immune cells, along with an increase in tissue macrophages, in all SSHTN groups compared with the control group. SSHTN mice had increased uterine pro-inflammatory macrophages, dendritic cells, natural killer cells, and CD4+ pro-inflammatory T cells, all of which were mitigated by HYD and AVE treatments. SSHTN promoted uterine inflammation, lymphatic vessel expansion, and altered hormone receptor expression, which were mitigated by pharmacological intervention, highlighting their therapeutic potential in preserving uterine homeostasis and improving reproductive health in women with SSHTN.<\/jats:p>","DOI":"10.1042\/cs20255879","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T14:19:16Z","timestamp":1759846756000},"page":"1629-1642","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood pressure reduction and anti-inflammatory macrophage augmentation attenuate uterine immune dysregulation and inflammation in mice with salt-sensitive hypertension"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8768-4681","authenticated-orcid":false,"given":"Shobana","family":"Navaneethabalakrishnan","sequence":"first","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany L.","family":"Goodlett","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah L.","family":"Smith","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyssa","family":"Cardenas","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Montalvo II","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella C.","family":"Peterson","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-8761","authenticated-orcid":false,"given":"Brett M.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"1Department of Medical Physiology, Texas A&M College of Medicine, Bryan, Texas, 77807, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"2025121011311744300_CS-2025-5879C1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0140-6736(05)17741-1","article-title":"Global burden of hypertension: analysis of worldwide data","volume":"365","author":"Kearney","year":"2005","journal-title":"Lancet"},{"key":"2025121011311744300_CS-2025-5879C2","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/S0140-6736(12)61766-8","article-title":"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"2025121011311744300_CS-2025-5879C3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0140-6736(14)61468-9","article-title":"Hypertension","volume":"386","author":"Poulter","year":"2015","journal-title":"Lancet"},{"key":"2025121011311744300_CS-2025-5879C4","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMra1212606","article-title":"Salt in Health and Disease \u2014 A Delicate Balance","volume":"368","author":"Kotchen","year":"2013","journal-title":"N. 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