{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:37:22Z","timestamp":1782149842408,"version":"3.54.5"},"reference-count":65,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:p> In pregnancy, \u03b1-adrenoceptor-mediated vasoconstriction is augmented in uterine radial arteries and is accompanied by underlying changes in smooth muscle (SM) Ca<jats:sup>2+<\/jats:sup> activity. This study aims to determine the Ca<jats:sup>2+<\/jats:sup> entry channels associated with altered vasoconstriction in pregnancy, with the hypothesis that augmented vasoconstriction involves transient receptor potential canonical type-3 (TRPC3) and L- and T-type voltage-dependent Ca<jats:sup>2+<\/jats:sup> channels. Immunohistochemistry showed TRPC3, L-type Ca<jats:sub>v<\/jats:sub>1.2 (as the \u03b11C subunit), T-type Ca<jats:sub>v<\/jats:sub>3.1 (\u03b11G), and Ca<jats:sub>v<\/jats:sub>3.2 (\u03b11H) localization to the uterine radial artery SM. Fluorescence intensity of TRPC3, Ca<jats:sub>v<\/jats:sub>1.2, and Ca<jats:sub>v<\/jats:sub>3.2 was increased, and Ca<jats:sub>v<\/jats:sub>3.1 decreased in radial artery SM from pregnant rats. Western blot analysis confirmed increased TRPC3 protein expression in the radial artery from pregnant rats. Pressure myography incorporating pharmacological intervention to examine the role of these channels in uterine radial arteries showed an attenuation of phenylephrine (PE)-induced constriction with Pyr3 {1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino]phenyl]-5-(trifluoromethyl)-1 H-pyrazole-4-carboxylic acid}-mediated TRPC3 inhibition or with nifedipine-mediated L-type channel block alone in vessels from pregnant rats; both effects of which were diminished in radial arteries from nonpregnant rats. Combined TRPC3 and L-type inhibition attenuated PE-induced constriction in radial arteries, and the residual vasoconstriction was reduced and abolished with T-type channel block with NNC 55-0396 in arteries from nonpregnant and pregnant rats, respectively. With SM Ca<jats:sup>2+<\/jats:sup> stores depleted and in the presence of PE, nifedipine, and NNC 55-0396, blockade of TRPC3 reversed PE-induced constriction. These data suggest that TRPC3 channels act synergistically with L- and T-type channels to modulate radial artery vasoconstriction, with the mechanism being augmented in pregnancy. <\/jats:p>","DOI":"10.1152\/ajpregu.00225.2013","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T04:06:54Z","timestamp":1376626014000},"page":"R917-R926","source":"Crossref","is-referenced-by-count":16,"title":["Enhanced contractility in pregnancy is associated with augmented TRPC3, L-type, and T-type voltage-dependent calcium channel function in rat uterine radial artery"],"prefix":"10.1152","volume":"305","author":[{"given":"Sevvandi","family":"Senadheera","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul P.","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Hilton","family":"Grayson","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Leader","sequence":"additional","affiliation":[{"name":"Leo Leader, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Tare","sequence":"additional","affiliation":[{"name":"Department of Physiology, Monash University, Melbourne, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy V.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun L.","family":"Sandow","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia;"},{"name":"Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydoore, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00476.2012"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-119495"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.179747"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198820"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.102780"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.125831"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000100367.45446.A3"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04855.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01126.2003"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.11.002"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70464-2"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.044149"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.04.026"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1994.267.3.H952"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gal110"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031428"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302983200"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.16.6980-6989.2005"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090641"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00490.2011"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00338.2003"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/951497"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1177\/1933719109340927"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/hc4301.098253"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.170845"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12038"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000256155.31133.49"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.250928"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.228262"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.196832"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70548-9"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.11"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000138952.16382.ad"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2010.06.002"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2010.05373.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/BF00592748"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.193300"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2011.00042"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(93)90519-O"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104271108"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00861.2004"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1818"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(77)90493-8"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr167"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02141.x"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2006.00647.x"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2888-2_36"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000019756.88731.83"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs208"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01937.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705408"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.11.026"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-2-00177.x"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00216.2007"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.007252"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs257"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.12.030"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.202077"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.280.5.C1184"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.173948"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01238.2005"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.07.038"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0720-y"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405908101"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980810)397:4<561::AID-CNE8>3.0.CO;2-#"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00225.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:18:17Z","timestamp":1567963097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00225.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,15]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,10,15]]}},"alternative-id":["10.1152\/ajpregu.00225.2013"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00225.2013","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,15]]}}}