{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:53:24Z","timestamp":1791921204757,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T00:00:00Z","timestamp":1379376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"Background and Purpose<\/jats:title>Transient receptor potential vanilloid type 4 (TRPV<\/jats:styled-content>4) channels are expressed in brain endothelial cells, but their role in regulating cerebrovascular tone under physiological and pathological conditions is still largely unknown.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Wild\u2010type (WT<\/jats:styled-content>) mice and mice that overexpress a mutated form of the human amyloid precursor protein (APP<\/jats:styled-content> mice, model of increased amyloid \u03b2), a constitutively active form of TGF\u2010\u03b21 (TGF<\/jats:styled-content> mice, model of cerebrovascular fibrosis) or both (APP<\/jats:styled-content>\/TGF<\/jats:styled-content> mice) were used. Dilations to the selective TRPV<\/jats:styled-content>4 channel opener GSK1016790A<\/jats:styled-content> (GSK<\/jats:styled-content>) or to ACh<\/jats:styled-content> were measured in posterior cerebral artery segments.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Both GSK<\/jats:styled-content>\u2010 and ACh<\/jats:styled-content>\u2010induced dilations virtually disappeared following endothelium denudation in WT<\/jats:styled-content> mice. These responses were impaired in vessels from APP<\/jats:styled-content>, TGF<\/jats:styled-content> and APP<\/jats:styled-content>\/TGF<\/jats:styled-content> mice compared with WT<\/jats:styled-content>. Pre\u2010incubation of WT<\/jats:styled-content> vessels with the selective TRPV<\/jats:styled-content>4 channel blocker HC<\/jats:styled-content>\u2010067047, or with small\u2010conductance (SK<\/jats:styled-content> channel, apamin) and\/or intermediate\u2010conductance (IK<\/jats:styled-content> channel, charybdotoxin, ChTx<\/jats:styled-content>) Ca<\/jats:roman><\/jats:styled-content>2+<\/jats:sup>\u2010sensitive K<\/jats:styled-content>+<\/jats:sup> channel blocker abolished GSK<\/jats:styled-content>\u2010induced dilations and massively decreased those induced by ACh<\/jats:styled-content>. These treatments had no or limited effects on ACh<\/jats:styled-content>\u2010induced dilation in vessels from APP<\/jats:styled-content>, TGF<\/jats:styled-content> or APP<\/jats:styled-content>\/TGF<\/jats:styled-content> mice, and IK<\/jats:styled-content> and SK<\/jats:styled-content> channel function was preserved in transgenic mice. Antioxidant superoxide dismutase or catalase normalized GSK<\/jats:styled-content>\u2010 and ACh<\/jats:styled-content>\u2010mediated dilations only in APP<\/jats:styled-content> brain arteries.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>We conclude that endothelial TRPV<\/jats:styled-content>4 channels mediate ACh<\/jats:styled-content>\u2010induced dilation in cerebral arteries, that they are impaired in models of cerebrovascular pathology and that they are sensitive, albeit in the reversible manner, to amyloid \u03b2\u2010induced oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12315","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T14:25:35Z","timestamp":1376490335000},"page":"661-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Endothelial TRPV<\/scp>4 channels mediate dilation of cerebral arteries: impairment and recovery in 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