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Alcohol in moderate\u2010to\u2010high concentrations constricts cerebral arteries and triggers brain ischemia. Here, we probed the ability of DHA to protect against alcohol action on cerebral artery diameter and on the activity of calcium\u2010\/voltage\u2010gated potassium channels of large conductance (BKs) in vasculature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Adult Sprague\u2013Dawley rats received daily oral DHA supplementation for up to 18\u201323\u2009weeks. Constriction of middle cerebral artery (MCA) pial branches was probed using a cranial window upon infusion of 50\u2009mM alcohol into the cerebral circulation. DHA and alcohol were also probed ex\u00a0vivo in MCAs upon vessel pressurization at 60\u2009mmHg. DHA's effect on alcohol\u2010induced inhibition of BK channels in MCA myocytes was probed using patch\u2010clamp recording of BK currents at physiological membrane voltage and intracellular calcium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DHA protected males but not females against alcohol\u2010induced vasoconstriction in\u00a0vivo. Oral DHA increased DHA levels in the MCA of male but not female rats. Arteries from male rats on control chow that were pressurized ex\u00a0vivo and perfused with 3 \u03bcM DHA lost their constriction by alcohol. Incubation of freshly isolated myocytes of male MCAs in DHA prevented alcohol\u2010induced inhibition of BK channels. However, DHA protection was absent when DHA was perfused to excised patches. DHA did not alter the amount of BK channel subunits within the myocyte plasmalemma of male MCAs. DHA protection against alcohol\u2010induced constriction persisted in arteries expressing BK channel with a mutation on a previously identified fatty acid\u2010sensing site.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>DHA protects against alcohol\u2010induced cerebral artery constriction and BK channel inhibition in a sexually dimorphic manner via cellular mechanisms in vascular myocytes. This action of DHA is independent of changes in BK subunit membrane levels and of a previously identified fatty acid\u2010sensing site in the BK channel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70073","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:15:54Z","timestamp":1748232954000},"page":"1396-1411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Docosahexaenoic acid protects against alcohol\u2010induced constriction of cerebral arteries and inhibition of vascular smooth muscle <scp>BK<\/scp> channels"],"prefix":"10.1111","volume":"49","author":[{"given":"Shiwani","family":"Thapa","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Mysiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Hawks","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tolley","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Division of Biostatistics The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M.","family":"Dopico","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-2319","authenticated-orcid":false,"given":"Anna N.","family":"Bukiya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, College of Medicine The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Alcohol. 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