{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:46:14Z","timestamp":1772113574088,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"4-5","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007179","name":"University of New Mexico","doi-asserted-by":"publisher","award":["NIH 2K12GM088021\u201011 (E.E.M.)"],"award-info":[{"award-number":["NIH 2K12GM088021\u201011 (E.E.M.)"]}],"id":[{"id":"10.13039\/100007179","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our previous work demonstrated that endothelial cell (EC) membrane cholesterol is reduced following 48\u2009h of chronic hypoxia (CH). CH couples endothelial transient receptor potential subfamily V member 4 (TRPV4) channels to muscarinic receptor signaling through an endothelium\u2010dependent hyperpolarization (EDH) pathway does not present in control animals. TRVPV4 channel activity has been shown to be regulated by membrane cholesterol. Hence, we hypothesize that acute manipulation of endothelial cell membrane cholesterol inversely determines the contribution of TRPV4 channels to endothelium\u2010dependent vasodilation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Sprague\u2013Dawley rats were exposed to ambient atmospheric (atm.) pressure or 48\u2010h of hypoxia (0.5\u00a0atm). Vasodilation to acetylcholine (ACh) was determined using pressure myography in gracilis arteries. EC membrane cholesterol was depleted using methyl\u2010\u03b2\u2010cyclodextrin (M\u03b2CD) and supplemented with M\u03b2CD\u2010cholesterol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibiting TRPV4 did not affect ACh\u2010induced vasodilation in normoxic controls. However, TRPV4 inhibition reduced resting diameter in control arteries suggesting basal activity. TRPV4 contributes to ACh\u2010induced vasodilation in these arteries when EC membrane cholesterol is depleted. Inhibiting TRPV4 attenuated ACh\u2010induced vasodilation in arteries from CH animals that exhibit lower EC membrane cholesterol than normoxic controls. EC cholesterol repletion in arteries from CH animals abolished the contribution of TRPV4 to ACh\u2010induced vasodilation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Endothelial cell membrane cholesterol impedes the contribution of TRPV4 channels in EDH\u2010mediated dilation. These results provide additional evidence for the importance of plasma membrane cholesterol content in regulating intracellular signaling and vascular function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.12774","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T10:04:38Z","timestamp":1654941878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Endothelial cell membrane cholesterol content regulates the contribution of <scp>TRPV4<\/scp> channels in <scp>ACh<\/scp>\u2010induced vasodilation in rat gracilis arteries"],"prefix":"10.1111","volume":"29","author":[{"given":"Emily E.","family":"Morin","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque New Mexico 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