Spironolactone Prevents Endothelial Nitric Oxide Synthase Uncoupling And Vascular Dysfunction Induced By Beta-adrenergic Overstimulation Role Of Perivascular Adipose Tissue

dc.creatorVictorio
dc.creatorJamaira A.; Clerici
dc.creatorStefano P.; Palacios
dc.creatorRoberto; Alonso
dc.creatorMaria J.; Vassallo
dc.creatorDalton V.; Jaffe
dc.creatorIris Z.; Rossoni
dc.creatorLuciana V.; Davel
dc.creatorAna P.
dc.date2016
dc.dateset
dc.date2017-11-13T13:55:11Z
dc.date2017-11-13T13:55:11Z
dc.date.accessioned2018-03-29T06:08:40Z
dc.date.available2018-03-29T06:08:40Z
dc.identifierHypertension . Lippincott Williams & Wilkins , v. 68, p. 726, 2016.
dc.identifier0194-911X
dc.identifier1524-4563
dc.identifierWOS:000381280400029
dc.identifier10.1161/HYPERTENSIONAHA.116.07911
dc.identifierhttp://hyper.ahajournals.org/content/early/2016/07/18/HYPERTENSIONAHA.116.07911
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/329595
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1366620
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionSustained stimulation of beta-adrenoceptors (beta-ARs) and activation of renin-angiotensin-aldosterone system are common features of cardiovascular diseases with rising sympathetic activation, including essential hypertension, myocardial infarction, and heart failure. In this study, we investigated the role of AT1 receptor and mineralocorticoid receptor (MR) in the vascular alterations caused by beta-AR overstimulation. beta-AR overstimulation with associated cardiac hypertrophy and increased vasoconstrictor response to phenylephrine in aorta were modeled in rats by 7-day isoproterenol treatment. The increased vasoconstrictor response to phenylephrine in this model was blunted by the MR antagonist spironolactone, but not by the AT1 receptor antagonist losartan, despite the blunting of cardiac hypertrophy with both drugs. Spironolactone, but not losartan, restored NO bioavailability in association with lower endothelial nitric oxide synthase-derived superoxide production, increased endothelial nitric oxide synthase dimerization, and aortic HSP90 upregulation. MR genomic and nongenomic functions were activated in aortas from isoproterenol-treated rats. Isoproterenol did not modify plasma levels of MR ligands aldosterone and corticosterone but rather increased perivascular adipose tissue-derived corticosterone in association with increased expression of 11 beta-hydroxysteroid dehydrogenase type 1. The anticontractile effect of aortic perivascular adipose tissue was impaired by beta-AR overstimulation and restored by MR blockade. These results suggest that activation of vascular MR signaling contributes to the vascular dysfunction induced by beta-AR overstimulation associated with endothelial nitric oxide synthase uncoupling. These findings reveal an additional explanation for the protective effects of MR antagonists in cardiovascular disorders with sympathetic activation.
dc.description68
dc.description3
dc.description726
dc.descriptionFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP Brazil) [14/07947-6, 11/15972-2]
dc.descriptionMinisterio de Educacion Cultura y Deporte [PHBP14/00001]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageEnglish
dc.publisherLippincott Williams & Wilkins
dc.publisherPhiladelphia
dc.relationHypertension
dc.rightsfechado
dc.sourceWOS
dc.subjectAdipose Tissue
dc.subjectAorta
dc.subjectBeta-adrenergic Receptors
dc.subjectEndothelial Nitric Oxide Synthase
dc.subjectLosartan
dc.subjectMineralocorticoid Receptor
dc.titleSpironolactone Prevents Endothelial Nitric Oxide Synthase Uncoupling And Vascular Dysfunction Induced By Beta-adrenergic Overstimulation Role Of Perivascular Adipose Tissue
dc.typeArtículos de revistas


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