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HFD alters perivascular adipose tissue (PVAT), which surrounds arteries and regulates vascular function. This study investigated the sex\u2010specific effects of HFD on PVAT\u2010mediated vascular dysfunction. Male and female Sprague\u2010Dawley rats were fed a normal chow diet (NCD) or HFD for 16\u2009weeks. Thoracic aortic PVAT was isolated, and PVAT adipokine expression and inflammatory markers were measured. We then assessed PVAT\u2010conditioned media effects on vasodilation, endothelial oxidative stress, and endothelial nitric oxide (NO) synthase. PVAT\u2010conditioned media from HFD female but not male rats impaired acetylcholine\u2010induced vasodilation in mesenteric arteries; however, it did not increase oxidative stress or decrease endothelial NO synthase activation in rat endothelial cells in\u00a0vitro. PVAT from HFD female rats had higher CD68 expression and acetyl\u2010NF\u2010\u03baB\/NF\u2010\u03baB ratio than PVAT from NCD female rats. Overall, HFD caused a greater PVAT\u2010induced impairment in vasodilation in female as compared to male rats, which aligns with the heightened cardiovascular risk in women consuming a HFD.<\/jats:p>","DOI":"10.14814\/phy2.70746","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:59:31Z","timestamp":1769605171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perivascular adipose tissue from female rats fed a high\u2010fat diet impaired mesenteric artery vasodilation"],"prefix":"10.14814","volume":"14","author":[{"given":"Gurneet S.","family":"Sangha","sequence":"first","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland College Park  College Park Maryland USA"},{"name":"Department of Biomedical Engineering University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan 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Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Barnes","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland College Park  College Park Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-2122","authenticated-orcid":false,"given":"Alisa M.","family":"Clyne","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland College Park  College Park Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"issue":"5","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000443885","article-title":"Effects of obesity on perivascular adipose tissue vasorelaxant function: Nitric oxide, inflammation and elevated systemic blood 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