{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:42:46Z","timestamp":1777434166466,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T00:00:00Z","timestamp":1512000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0802004"],"award-info":[{"award-number":["G0802004"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/07\/056"],"award-info":[{"award-number":["FS\/07\/056"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiovascular disease is the world's leading cause of morbidity and mortality, with high blood pressure (<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>) contributing to increased severity and number of adverse outcomes. Plasma membrane calcium <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase 4 (<jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4) has been previously shown to modulate systemic <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>. However, published data are conflicting, with both overexpression and inhibition of <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 <jats:italic>in\u00a0vivo<\/jats:italic> shown to increase arterial contractility. Hence, our objective was to determine the role of <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 in the regulation of <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and to further understand how <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 functionally regulates <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> using a novel specific inhibitor to <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4, aurintricarboxylic acid (<jats:styled-content style=\"fixed-case\">ATA<\/jats:styled-content>). Our approach assessed conscious <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and contractility of resistance arteries from <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 global knockout (<jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice compared to wild\u2010type animals. Global ablation of <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 had no significant effect on <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>, arterial structure or isolated arterial contractility. <jats:styled-content style=\"fixed-case\">ATA<\/jats:styled-content> treatment significantly reduced <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and arterial contractility in wild\u2010type mice but had no significant effect in <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice. The effect of <jats:styled-content style=\"fixed-case\">ATA<\/jats:styled-content><jats:italic>in\u00a0vivo<\/jats:italic> and <jats:italic>ex\u00a0vivo<\/jats:italic> was abolished by the neuronal nitric oxide synthase (<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>) inhibitor Vinyl\u2010<jats:sc>l<\/jats:sc>\u2010<jats:styled-content style=\"fixed-case\">NIO<\/jats:styled-content>. Thus, this highlights differences in the effects of <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 ablation and acute inhibition on the vasculature. Importantly, for doses here used, we show the vascular effects of <jats:styled-content style=\"fixed-case\">ATA<\/jats:styled-content> to be specific for <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4 and that <jats:styled-content style=\"fixed-case\">ATA<\/jats:styled-content> may be a further experimental tool for elucidating the role of <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>4.<\/jats:p>","DOI":"10.1111\/jcmm.13371","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T08:06:39Z","timestamp":1512029199000},"page":"861-872","source":"Crossref","is-referenced-by-count":6,"title":["Acute inhibition of <scp>PMCA<\/scp>4, but not global ablation, reduces blood pressure and arterial contractility via a <scp>nNOS<\/scp>\u2010dependent mechanism"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7584-7749","authenticated-orcid":false,"given":"Sophronia","family":"Lewis","sequence":"first","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Little","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Baudoin","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukhpal","family":"Prehar","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludwig","family":"Neyses","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare","family":"Austin","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Cardiovascular Sciences The University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,30]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Global status report on noncommunicable diseases 2010","author":"Alwan A","year":"2011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11403-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91285-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.89.1.49"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"1362\u2010A","DOI":"10.1136\/bmj.331.7529.1362","article-title":"The ageing population\u00a0of the United Kingdom and cardiovascular disease","volume":"331","author":"Majeed A","year":"2005","journal-title":"Br Med J"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01080.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.01.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.61.2.181"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00029.2008"},{"key":"e_1_2_8_11_1","first-page":"808353","article-title":"Pathophysiology of vascular remodeling in hypertension","volume":"2013","author":"Renna NF","year":"2013","journal-title":"Int J Hypertens"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12046"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.08.010"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-011-4199-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307606200"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00518.2002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2014.920393"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000092142.19896.D9"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00573.2005"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00140.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1387.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200104131"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1591"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513341200"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.07.007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11074"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312599200"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.15.8882"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.18433\/J3PG68","article-title":"Optimisation and validation of a high throughput screening compatible assay to identify inhibitors of the plasma membrane calcium ATPase pump\u2013a novel therapeutic target for contraception and malaria","volume":"16","author":"Mohamed TM","year":"2013","journal-title":"J Pharm Pharm Sci"},{"key":"e_1_2_8_31_1","first-page":"1582","article-title":"Age\u2010related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin\u20101 knockout","volume":"5","author":"Hausman N","year":"2011","journal-title":"J Cell Mol Med"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.12.016"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.03.011"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31818d7e5a"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14717.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020966"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01457.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.290411"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00440.2005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2000.105454"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0348-6"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1139\/y05-075"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160062"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.12.1271"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156793"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.008"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.08.011"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.682"},{"key":"e_1_2_8_49_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/978-1-60761-700-6_18","article-title":"Measurement of plasma membrane calcium\u2010calmodulin\u2010dependent ATPase (PMCA) activity","volume":"637","author":"Mohamed TM","year":"2010","journal-title":"Methods Mol Biol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.643791"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.12.007"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.2741\/1684"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0773-9"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0815-2"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0455-z"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.533638"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404628200"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.06.098"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00335.x"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13371","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T12:12:30Z","timestamp":1695903150000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,30]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/jcmm.13371"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13371","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,30]]}}}