{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T18:57:15Z","timestamp":1784746635820,"version":"3.55.0"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T00:00:00Z","timestamp":1522368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A is essential for Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:sup>\u2212<\/jats:sup> conductance in vascular smooth muscle. The importance of <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A for agonist\u2010induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A might have a complex cellular function beyond being essential for the Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:sup>\u2212<\/jats:sup> conductance, for example modulation of Ca<jats:sup>2+<\/jats:sup> channel expression. Mice with constitutive, smooth muscle\u2010specific expression of si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> directed against <jats:italic>Tmem16a<\/jats:italic> (transgenic mice, <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>) were generated. Isometric constrictions of isolated aorta, mesenteric, femoral and tail arteries from <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice were compared with wild\u2010types. Protein expression was analysed by Western blots. Blood pressure and heart rate were studied telemetrically. Significant <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A down\u2010regulation was seen in aorta and tail arteries, while no changes were detected in mesenteric and femoral arteries. Contractile responses of mesenteric and femoral arteries from <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> and wild\u2010type mice were not different. Aorta from <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice showed reduced agonist\u2010induced constriction, while their responses to elevated K<jats:sup>+<\/jats:sup> were unchanged. Tail arteries from <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice also constricted less to adrenergic stimulation than wild\u2010types. Surprisingly, tail arteries from <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice constricted less to elevated K<jats:sup>+<\/jats:sup> too and were more sensitive to nifedipine\u2010induced relaxation. Consistently, <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A down\u2010regulation in tail arteries was associated with reduction in <jats:styled-content style=\"fixed-case\">CACNA<\/jats:styled-content>1C protein (i.e. vascular L\u2010type Ca<jats:sup>2+<\/jats:sup> channel) expression. No differences in blood pressure and heart rate between the groups were seen. This study suggests a complex contribution of <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A in vascular function. We suggest that <jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>16A modulates arterial contractility, at least in part, indirectly via regulation of <jats:styled-content style=\"fixed-case\">CACNA<\/jats:styled-content>1C expression.<\/jats:p>","DOI":"10.1111\/bcpt.12984","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T19:35:40Z","timestamp":1518550540000},"page":"30-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Variable Contribution of <scp>TMEM<\/scp>16A to Tone in Murine Arterial Vasculature"],"prefix":"10.1111","volume":"123","author":[{"given":"Anders Bisgaard","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Black","family":"Joergensen","sequence":"additional","affiliation":[{"name":"Department of 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