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Thus, the primary goal of the present study was to explore the effects of choline on the function of mesenteric arteries following<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>, with a major focus on<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">CaMKII<\/jats:styled-content>) regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Rats were given choline (10\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v.) and then the superior mesenteric artery was occluded for 60\u2009min (ischaemia), followed by 90\u2009min of reperfusion. The<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content><jats:sub>3<\/jats:sub>receptor antagonist, 4\u2010diphenylacetoxy\u2010N\u2010methylpiperidine methiodide (4\u2010<jats:styled-content style=\"fixed-case\">DAMP),<\/jats:styled-content>was injected (0.12\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v.) 5\u2009min prior to choline treatment. Vascular function was examined in rings of mesenteric arteries isolated after the reperfusion procedure. Vascular superoxide anion production,<jats:styled-content style=\"fixed-case\">CaMKII<\/jats:styled-content>and the levels of<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010cycling proteins were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Choline treatment attenuated<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010induced vascular dysfunction, blocked elevations in the levels of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) and decreased the up\u2010regulated expression of oxidised<jats:styled-content style=\"fixed-case\">CaMKII<\/jats:styled-content>and phosphorylated<jats:styled-content style=\"fixed-case\">CaMKII<\/jats:styled-content>. In addition, choline reversed the abnormal expression of<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010cycling proteins, including<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>a<jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>exchanger, inositol 1,4,5\u2010trisphosphate receptor, sarcoplasmic reticulum<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase and phospholamban. All of these cholinergic effects of choline were abolished by 4\u2010<jats:styled-content style=\"fixed-case\">DAMP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data suggest that inhibition of the<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\u2010mediated<jats:styled-content style=\"fixed-case\">CaMKII<\/jats:styled-content>pathway and modulation of<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010cycling proteins may be novel mechanisms underlying choline\u2010induced vascular protection. These results represent a significant addition to the understanding of the pharmacological roles of<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content><jats:sub>3<\/jats:sub>receptors in the vasculature, providing a new therapeutic strategy for<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010induced vascular injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23\">http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13183","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T06:12:54Z","timestamp":1431065574000},"page":"5619-5633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Activation of<scp>M<\/scp><sub>3<\/sub>cholinoceptors attenuates vascular injury after ischaemia\/reperfusion by inhibiting the<scp><scp>Ca<\/scp><\/scp><sup>2+<\/sup>\/calmodulin\u2010dependent protein kinase<scp>II<\/scp>pathway"],"prefix":"10.1111","volume":"172","author":[{"given":"Xing\u2010Zhu","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pharmacology Xi'an Jiaotong University Health Science Center 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