Sökning: onr:"swepub:oai:DiVA.org:uu-348111" > Vascular dysfunctio...
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000 | 04450naa a2200445 4500 | |
001 | oai:DiVA.org:uu-348111 | |
003 | SwePub | |
008 | 180411s2018 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3481112 URI |
024 | 7 | a https://doi.org/10.1038/s41598-018-21087-52 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Cat, Aurelie Nguyen Dinhu Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.4 aut |
245 | 1 0 | a Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling |
264 | c 2018-02-13 | |
264 | 1 | b NATURE PUBLISHING GROUP,c 2018 |
338 | a electronic2 rdacarrier | |
520 | a Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+. This was associated with enhanced vascular MR signaling. Norepinephrine (NE)-induced contraction was increased in arteries from db/db mice. These responses were attenuated in mice treated with canrenoate or fasudil. Db/db mice displayed hypertrophic remodeling and increased arterial stiffness, improved by MR blockade. Vascular calcium sensitivity was similar between depolarized arteries from db/+ and db/db. Vascular hypercontractility in db/db mice was associated with increased myosin light chain phosphorylation and reduced expression of PKG-1 alpha. Vascular RhoA/ROCK signaling and expression of pro-inflammatory and pro-fibrotic markers were exaggerated in db/db mice, effects that were attenuated by MRA. Fasudil, but not MRA, improved vascular insulin sensitivity in db/db mice, evidenced by normalization of Irs1 phosphorylation. Our data identify novel pathways involving MR-RhoA/ROCK-PKG-1 that underlie vascular dysfunction and injury in diabetic mice. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng |
700 | 1 | a Callera, Glaucia E.u Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.4 aut |
700 | 1 | a Friederich, Malou,d 1983-u Uppsala universitet,Institutionen för medicinsk cellbiologi,Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland4 aut0 (Swepub:uu)malfr648 |
700 | 1 | a Sanchez, Anau Univ Complutense, Fac Farm, Dept Fisiol, Madrid, Spain.4 aut |
700 | 1 | a Dulak-Lis, Maria Gabrielau Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.4 aut |
700 | 1 | a Tsiropoulou, Sofiau Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.4 aut |
700 | 1 | a Montezano, Augusto C.u Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.4 aut |
700 | 1 | a He, Yingu Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.4 aut |
700 | 1 | a Briones, Ana M.u Univ Autonoma Madrid, CIBER Enfermedades Cardiovasc, Sch Med, Dept Pharmacol, Madrid, Spain.4 aut |
700 | 1 | a Jaisser, Fredericu Ctr Rech Cordeliers, INSERM Team 1 1138, Paris, France.4 aut |
700 | 1 | a Touyz, Rhian M.u Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.;Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.4 aut |
710 | 2 | a Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.b Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.4 org |
773 | 0 | t Scientific Reportsd : NATURE PUBLISHING GROUPg 8q 8x 2045-2322 |
856 | 4 | u https://doi.org/10.1038/s41598-018-21087-5y Fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1196780/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u https://www.nature.com/articles/s41598-018-21087-5.pdf |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-348111 |
856 | 4 8 | u https://doi.org/10.1038/s41598-018-21087-5 |
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