期刊
FRONTIERS IN PHYSIOLOGY
卷 6, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2015.00269
关键词
type 2 diabetes; aldosterone; mineralocorticoid receptor; vascular; oxidative stress
类别
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/08216-2]
- CRID
- FAPESP-AUF [2010/52214-6]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro oxidative and pro inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepR(db)/LepR(db) (db/db)] mice, a model of DM2, and their counterpart controls [LepR(db)/Lep(R+)(db/+) mice] received spironolactone (50 mg/kg body weight/day) or vehicle (ethanol 1%) via oral per gavage for 6 weeks. Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser(1177)) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 and catalase expression, improved sodium nitroprusside and BAY 41-2272-induced relaxation, and increased soluble guanylyl cyclase (sGC) beta, subunit expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据