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This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2<jats:sup>+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK<jats:sub>Ca<\/jats:sub>) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BK<jats:sub>Ca<\/jats:sub>currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage\/Ca<jats:sup>2+<\/jats:sup>sensitivity of BK<jats:sub>Ca<\/jats:sub>channels. BK<jats:sub>Ca<\/jats:sub>\u03b1-subunit expression was unchanged, BK<jats:sub>Ca<\/jats:sub>\u03b21-subunit and sensitivity of BK<jats:sub>Ca<\/jats:sub>to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BK<jats:sub>Ca<\/jats:sub>in the MA. Simultaneous [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>fluorescence and vasoconstriction testing showed reduced Ca<jats:sup>2+<\/jats:sup>, leading to diminished BK<jats:sub>Ca<\/jats:sub>activation via ryanodine receptor Ca<jats:sup>2+<\/jats:sup>release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BK<jats:sub>Ca<\/jats:sub>, providing new information for further understanding increased risks of hypertension in developmental origins.<\/jats:p>","DOI":"10.1038\/srep13225","type":"journal-article","created":{"date-parts":[[2015,8,17]],"date-time":"2015-08-17T11:13:42Z","timestamp":1439810022000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring"],"prefix":"10.1038","volume":"5","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinqin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bailin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiping","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhice","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,8,17]]},"reference":[{"key":"BFsrep13225_CR1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0140-6736(86)91340-1","volume":"1","author":"DJ Barker","year":"1986","unstructured":"Barker, D. 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