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dc.contributor.authorWei, Yongzhongeng
dc.contributor.authorWhaley-Connell, Adam T.eng
dc.contributor.authorHabibi, Javad, 1947-eng
dc.contributor.authorRehmer, Jennaeng
dc.contributor.authorRehmer, Nathaneng
dc.contributor.authorPatel, Kamlesh D.eng
dc.contributor.authorHayden, Melvineng
dc.contributor.authorDeMarco, Vincent G.eng
dc.contributor.authorFerrario, Carlos M.eng
dc.contributor.authorIbdah, Jamal A.eng
dc.contributor.authorSowers, James R. (James Russell), 1942-eng
dc.date.issued2008-12eng
dc.descriptionThis article may also be found at the publisher's website at http://hyper.ahajournals.org/cgi/content/abstract/53/2/158?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=habibi&searchid=1&FIRSTINDEX=0&resourcetype=HWCITeng
dc.description.abstractEmerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure-lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine473 phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine136 and expression of Bcl-2 and Bcl-xL, decreasing cytochrome c release and BAD expression, and suppressing caspase-3 activation. Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1 receptor, and MR in Ren2 vasculature. These results demonstrate that MR antagonism protects the vasculature from aldosterone-induced vascular apoptosis and structural injury via rescuing protein kinase B activation, independent of blood pressure effects.eng
dc.identifier.citationHypertension 2009;53;158-165eng
dc.identifier.otherDOI: 10.1161/HYPERTENSIONAHA.108.121954eng
dc.identifier.urihttp://hdl.handle.net/10355/3767eng
dc.languageEnglisheng
dc.publisherAmerican Heart Associationeng
dc.relation.ispartofElectron Microscopy Core Facility publications (MU)eng
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Christopher S. Bond Life Sciences Center. Electron Microscopy Core Facilityeng
dc.source.urihttp://www.emc.missouri.edu/recpub.htmeng
dc.source.urihttp://hyper.ahajournals.org/cgi/reprint/53/2/158?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=habibi&searchid=1&FIRSTINDEX=0&resourcetype=HWCITeng
dc.subject.lcshSteroid hormones -- Receptors -- Effect of drugs oneng
dc.subject.lcshAldosteroneeng
dc.subject.lcshOxidative stresseng
dc.titleMineralocorticoid Receptor Antagonism Attenuates Vascular Apoptosis and Injury via Rescuing Protein Kinase B Activationeng
dc.typeArticleeng


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