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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\u2009mg\/kg\/day, 4 weeks) or ROCK inhibitor, fasudil (30\u2009mg\/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\u03b1. 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.<\/jats:p>","DOI":"10.1038\/s41598-018-21087-5","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T10:54:51Z","timestamp":1518000891000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Vascular dysfunction in obese diabetic db\/db mice involves the interplay between aldosterone\/mineralocorticoid receptor and Rho kinase signaling"],"prefix":"10.1038","volume":"8","author":[{"given":"Aurelie","family":"Nguyen Dinh Cat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glaucia E.","family":"Callera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malou","family":"Friederich-Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-8702","authenticated-orcid":false,"given":"Ana","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriela","family":"Dulak-Lis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Tsiropoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto C.","family":"Montezano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Briones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Jaisser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-0887","authenticated-orcid":false,"given":"Rhian M.","family":"Touyz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"21087_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/j.1550-8528.1999.tb00418.x","volume":"7","author":"TL Goodfriend","year":"1999","unstructured":"Goodfriend, T. 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