{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:05:24Z","timestamp":1792148724050,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T00:00:00Z","timestamp":1393804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Binge drinking represents the major form of excessive alcohol (ethanol [<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>]) consumption in the <jats:styled-content style=\"fixed-case\">United States<\/jats:styled-content>. Episodic (such as binge) drinking results in blood alcohol levels (<jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content>) of 18 to 80\u00a0mM and leads to alcohol\u2010induced cerebral artery constriction (<jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content> was shown to arise from <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>\u2010induced inhibition of large\u2010conductance, calcium\/voltage\u2010gated potassium (<jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content>) channels in the vascular smooth muscle. Factors that modulate <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel\u2010mediated <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content> remain largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats were placed on high\u2010cholesterol (2% of cholesterol) diet for 18 to 23\u00a0weeks. Their littermates were placed on control iso\u2010caloric diet. <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content> was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl\u2010<jats:italic>\u03b2<\/jats:italic>\u2010cyclodextrin to reverse dietary\u2010induced accumulation of cholesterol. <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel function in pressurized cerebral artery was assessed using selective <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel blocker paxilline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Within 5\u00a0minutes of 50\u00a0mM <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content> injection into carotid artery in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole constriction was significantly reduced in rats on high\u2010cholesterol diet, resulting in only 10% reduction in diameter. <jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content> in both groups, however, remained the same. Significant reduction in <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content> in group on high\u2010cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60\u00a0mmHg, this reduction remaining after endothelium removal. Cholesterol level in de\u2010endothelialized cerebral arteries was significantly increased in rats on high\u2010cholesterol diet. Removal of excessive cholesterol content restored <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content> to the level observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel\u2010forming and accessory, smooth muscle\u2010specific <jats:italic>\u03b2<\/jats:italic>1 subunit in freshly isolated cerebral artery myocyte showed that high\u2010cholesterol diet did not down\u2010regulate surface presence of <jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> protein. However, paxilline\u2010induced cerebral artery constriction was diminished in arteries from rats on high\u2010cholesterol diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data indicate that dietary cholesterol protects against <jats:styled-content style=\"fixed-case\">AICAC<\/jats:styled-content>. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content> target\u2014<jats:styled-content style=\"fixed-case\">BK<\/jats:styled-content> channel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12373","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T16:48:39Z","timestamp":1393865319000},"page":"1216-1226","source":"Crossref","is-referenced-by-count":29,"title":["Dietary Cholesterol Protects Against Alcohol\u2010Induced Cerebral Artery Constriction"],"prefix":"10.1111","volume":"38","author":[{"given":"Anna","family":"Bukiya","sequence":"first","affiliation":[{"name":"Department of Pharmacology College of Medicine University of Tennessee Health Science Center Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro 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