{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:33:49Z","timestamp":1792046029535,"version":"4.4.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1302200"],"award-info":[{"award-number":["2016YFC1302200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873544"],"award-info":[{"award-number":["81873544"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Purposes<\/jats:bold>: Since the role of store-operated calcium entry (SOCE) in endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of mesenteric arteries in health and colitis is not fully understood, cyclopiazonic acid (CPA), a specific inhibitor of the sarco(endo) plasmic reticulum calcium-ATPases (SERCA), was used as a SOCE activator to investigate its role in normal mice and its alteration in colitis mice.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: The changes in Ca<jats:sup>2+<\/jats:sup> signaling in vascular endothelial cells (VEC) were examined by single cell Ca<jats:sup>2+<\/jats:sup> imaging and tension of mesenteric arteries in response to CPA were examined using Danish DMT520A microvascular measuring system.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: CPA activated the SOCE through depletion of the endoplasmic reticulum (ER) Ca<jats:sup>2+<\/jats:sup> in endothelial cells. CPA had a concentration-dependent vasorelaxing effect in endothelium-intact mesenteric arteries, which was lost after endothelial removal. Both nitric oxide (NO) and prostacyclin (PGI<jats:sub>2<\/jats:sub>) inhibitors did not affect CPA-induced vasorelaxation; however, after both NO and PGI<jats:sub>2<\/jats:sub> were inhibited, K<jats:sub>Ca<\/jats:sub> channel blocker [10 mM tetraethylammonium chloride (TEA)] inhibited CPA-induced vasorelaxation while K<jats:sub>Ca<\/jats:sub> channel activator (0.3 \u03bcM SKA-31) promoted it. Two SOCE blockers [30 \u03bcM SKF96365 and 100 \u03bcM flufenamic acid (FFA)], and an Orai channel blocker (30 \u03bcM GSK-7975A) inhibited this vasorelaxation. The inhibition of both Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase (NKA) and Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>-exchange (NCX) also inhibited CPA-induced vasorelaxation. Finally, the CPA involved in EDH-induced vasorelaxation by the depletion of ER Ca<jats:sup>2+<\/jats:sup> of mesenteric arteries was impaired in colitis mice.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: Depletion of ER Ca<jats:sup>2+<\/jats:sup> by CPA induces a vasorelaxation of mesenteric arteries that is mediated through EDH mechanism and invokes the activation of SOCE. The CPA-induced endothelium-dependent dilation is impaired in colitis which may limit blood perfusion to the intestinal mucosa.<\/jats:p>","DOI":"10.3389\/fphys.2021.639857","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T04:19:32Z","timestamp":1615263572000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Cyclopiazonic Acid-Induced Ca2+ Store Depletion Initiates Endothelium-Dependent Hyperpolarization-Mediated Vasorelaxation of Mesenteric Arteries in Healthy and Colitis Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Lu Yun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1097\/00024382-199711000-00011","article-title":"Sympathetic and renin-angiotensin activation during graded hypovolemia in pigs: impact on mesenteric perfusion and duodenal mucosal function","volume":"8","author":"Aneman","year":"1997","journal-title":"Shock"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/cvr\/cvp105","article-title":"Extracellular acidosis suppresses endothelial function by inhibiting store-operated Ca2+ entry via non-selective cation channels","volume":"83","author":"Asai","year":"2009","journal-title":"Cardiovasc. 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