{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:34:51Z","timestamp":1776760491640,"version":"3.51.2"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inserm"},{"name":"Inserm and Sorbonne University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Notch3 plays an important role in the differentiation and development of vascular smooth muscle cells. Mice lacking Notch3 show deficient renal autoregulation. The aim of the study was to investigate the mechanisms involved in the Notch3-mediated control of renal vascular response. To this end, renal resistance vessels (afferent arterioles) were isolated from Notch3\u2212\/\u2212 and wild-type littermates (WT) and stimulated with angiotensin II (ANG II). Contractions and intracellular Ca2+ concentrations were blunted in Notch3\u2212\/\u2212 vessels. ANG II responses in precapillary muscle arterioles were similar between the WT and Notch3\u2212\/\u2212 mice, suggesting a focal action of Notch3 in renal vasculature. Abolishing stored Ca2+ with thapsigargin reduced Ca2+ responses in the renal vessels of the two strains, signifying intact intracellular Ca2+ mobilization in Notch3\u2212\/\u2212. EGTA (Ca2+ chelating agent), nifedipine (L-type channel-blocker), or mibefradil (T-type channel-blocker) strongly reduced contraction and Ca2+ responses in WT mice but had no effect in Notch3\u2212\/\u2212 mice, indicating defective Ca2+ entry. Notch3\u2212\/\u2212 vessels responded normally to KCl-induced depolarization, which activates L-type channels directly. Differential transcriptomic analysis showed a major down-regulation of Cacna1h gene expression, coding for the \u03b11H subunit of the T-type Ca2+ channel, in Notch3\u2212\/\u2212 vessels. In conclusion, renal resistance vessels from Notch3\u2212\/\u2212 mice display altered vascular reactivity to ANG II due to deficient Ca2+-entry. Consequently, Notch3 is essential for proper excitation\u2013contraction coupling and vascular-tone regulation in the kidney.<\/jats:p>","DOI":"10.3390\/ijms232416068","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deletion of Notch3 Impairs Contractility of Renal Resistance Vessels Due to Deficient Ca2+ Entry"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9650-2747","authenticated-orcid":false,"given":"Frank","family":"Helle","sequence":"first","affiliation":[{"name":"INSERM UMR S 1155, H\u00f4pital Tenon, 75020 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-1099","authenticated-orcid":false,"given":"Michael","family":"Hultstr\u00f6m","sequence":"additional","affiliation":[{"name":"Renal Research Group, Institute of Medicine, University of Bergen, 5007 Bergen, Norway"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"},{"name":"Department of Biomedicine, University of Bergen, 5007 Bergen, Norway"},{"name":"Integrative Physiology, Department of Medical Cell Biology, Uppsala University, 75105 Uppsala, Sweden"},{"name":"Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, 75105 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Kavvadas","sequence":"additional","affiliation":[{"name":"INSERM UMR S 1155, H\u00f4pital Tenon, 75020 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarne","family":"Iversen","sequence":"additional","affiliation":[{"name":"Renal Research Group, Institute of Medicine, University of Bergen, 5007 Bergen, Norway"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-7900","authenticated-orcid":false,"given":"Christos E.","family":"Chadjichristos","sequence":"additional","affiliation":[{"name":"INSERM UMR S 1155, H\u00f4pital Tenon, 75020 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Chatziantoniou","sequence":"additional","affiliation":[{"name":"INSERM UMR S 1155, H\u00f4pital Tenon, 75020 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcp.10208","article-title":"HES and HERP families: Multiple effectors of the Notch signaling pathway","volume":"194","author":"Iso","year":"2003","journal-title":"J. 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