{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T12:40:24Z","timestamp":1775997624556,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The striking increase of uterine blood flow during pregnancy is essential for normal fetal development as well as for cardiovascular well\u2010being of the mother. Yet, the underlying mechanisms of pregnancy\u2010mediated vasodilatation of the uterine artery are not fully understood. In this study, we test the hypothesis that Rad, a monomeric G protein, is a novel regulatory mechanism in inhibiting Ca<jats:sub>V<\/jats:sub>1.2 channel currents in uterine artery haemodynamic adaptation to pregnancy in a sheep model. We found that pregnancy significantly upregulates Rad expression and decreases Ca<jats:sub>V<\/jats:sub>1.2 channel currents in uterine arterial smooth muscle cells. <jats:italic>Rad<\/jats:italic> knockdown <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> increases Ca<jats:sub>V<\/jats:sub>1.2 activity and channel window currents by reducing steady\u2010state inactivation in uterine arteries of pregnant sheep, recapitulating the phenotype of uterine arteries in non\u2010pregnant animals. Moreover, <jats:italic>Rad<\/jats:italic> knockdown <jats:italic>in vivo<\/jats:italic> in pregnant sheep enhances myogenic tone and phenylephrine\u2010induced vasoconstriction of uterine arteries. Whereas knockdown of <jats:italic>Rad<\/jats:italic> has no effect on mesenteric arterial Ca<jats:sub>V<\/jats:sub>1.2 channel activity and mean arterial blood pressure, it significantly increases uterine vascular resistance and decreases uterine artery blood flow. Our study reveals a novel cause\u2010and\u2010effect mechanism of Rad in pregnancy\u2010induced suppression of Ca<jats:sub>V<\/jats:sub>1.2 channel activity in uterine arteries to facilitate increased uterine blood flow, providing new insights into fundamental mechanisms of uterine haemodynamic adaptation to pregnancy.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16457-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Pregnancy suppresses Ca<jats:sub>V<\/jats:sub>1.2 channel currents in uterine arterial smooth muscle cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rad, a monomeric G protein, is upregulated in uterine arteries of pregnant sheep.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>Rad<\/jats:italic> knockdown <jats:italic>ex vivo<\/jats:italic> or <jats:italic>in vivo<\/jats:italic> increases Ca<jats:sub>V<\/jats:sub>1.2 channel currents in uterine arteries from pregnant ewes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>In vivo<\/jats:italic> knockdown of <jats:italic>Rad<\/jats:italic> elevates uterine vascular resistance and decreases uterine blood flow in pregnant sheep.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The study reveals a novel mechanism of Rad in pregnancy\u2010induced suppression of Ca<jats:sub>V<\/jats:sub>1.2 channel activity in uterine arterial haemodynamic adaptation to pregnancy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287334","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T20:09:36Z","timestamp":1732910976000},"page":"6729-6744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rad\u2010mediated inhibition of Ca<sub>V<\/sub>1.2 channel activity contributes to uterine artery haemodynamic adaptation to pregnancy"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-9541","authenticated-orcid":false,"given":"Xiang\u2010Qun","family":"Hu","sequence":"first","affiliation":[{"name":"Lawrence D. 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