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The hypothesis that hypoxia and ischemic stroke induce EC\u2010BK<jats:sub>Ca<\/jats:sub> in cerebral arteries was examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry analyzed BK<jats:sub>Ca<\/jats:sub> expression in EC and smooth muscle (SM) of the middle\u2010cerebral artery (MCA) from rat, piglet, and mouse, and pial arteriole of human. Pressure myography with pharmacological intervention characterized EC\u2010BK<jats:sub>Ca<\/jats:sub> and TRPV4 function in rat MCA. Electron microscopy determined caveolae density and vessel properties in rat and mouse MCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In rat, pig, and human cerebral vessels, EC\u2010BK<jats:sub>Ca<\/jats:sub> was absent in normoxia; present after <jats:italic>chronic<\/jats:italic> (rat) and <jats:italic>acute<\/jats:italic> hypoxia (pig), post\u2010ischemic stroke in human vessels, and after endothelin\u20101\u2010induced stroke in rats. Mouse MCA EC\u2010BK<jats:sub>Ca<\/jats:sub> expression increased after <jats:italic>acute<\/jats:italic> hypoxia. In rat MCA post\u2010hypoxia and stroke, EC and SMC caveolae density increased, with reduced medial thickness, and unchanged diameter. Caveolae and BK<jats:sub>Ca<\/jats:sub> did not colocalize. In rat MCA, iberiotoxin (IbTx) potentiated pressure\u2010induced tone in hypoxia\/stroke, but not in normoxia. In normoxia, overall MCA tone was unaffected by endothelial removal, but was increased in hypoxia\/stroke, where there was no additive effect of endothelial removal and IbTx on tone. Functional TRPV4 was expressed in EC of rat MCA post\u2010stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In post\u2010hypoxia\/stroke, but not in normoxia, EC\u2010BK<jats:sub>Ca<\/jats:sub> contribute to the regulation of MCA tone. Identifying unique up\u2010 and downstream signaling mechanisms associated with EC\u2010BK<jats:sub>Ca<\/jats:sub> is a potential therapeutic target to control blood flow post\u2010hypoxia\/stroke.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70030","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T11:01:27Z","timestamp":1742727687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial <scp>BK<\/scp>(Ca) channels\u2014Lessons from rat, pig, mouse, and human"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-4409","authenticated-orcid":false,"given":"Christian","family":"Staehr","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Health Aarhus University  Aarhus Denmark"},{"name":"Department of Anaesthesiology and Intensive Care Aarhus 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