ArticleHypertension (Dallas, Tex. : 1979)2009
Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation.
Article in Hypertension (Dallas, Tex. : 1979), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Spironolactone and hydrochlorothiazide decrease vascular stiffness and blood pressure in geriatric hypertension.Journal of the American Geriatrics Society · 2010Trial
- The impact of mineralocorticoid receptor antagonists on fat mass and fat metabolism.Journal of endocrinological investigation · 2026Review
- Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.Life (Basel, Switzerland) · 2025Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Atrial Fibrillation and Aortic Ectasia as Complications of Primary Aldosteronism: Focus on Pathophysiological Aspects.International journal of molecular sciences · 2022Review
- Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism.Frontiers in cardiovascular medicine · 2021Review
- The Effects of Salt and Glucose Intake on Angiotensin II and Aldosterone in Obese and Nonobese Patients with Essential Hypertension.International journal of hypertension · 2020Article
- Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword.Cardiovascular diabetology · 2018Review
- The emerging role of aldosterone/mineralocorticoid receptors in the pathogenesis of erectile dysfunction.Endocrine · 2018Review
- Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets.British journal of pharmacology · 2017Review
- Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice.Cardiovascular diabetology · 2016Article
- Diabetes mellitus and vascular disease.Hypertension (Dallas, Tex. : 1979) · 2013Article
- Oxidative stress in the cardiorenal metabolic syndrome.Current hypertension reports · 2012Review
- Ultrastructure Study of Transgenic Ren2 Rat Aorta - Part 1: Endothelium and Intima.Cardiorenal medicine · 2012Article
- Mineralocorticoid receptor-dependent proximal tubule injury is mediated by a redox-sensitive mTOR/S6K1 pathway.American journal of nephrology · 2012Article
- Mineralocorticoid receptor blockade improves diastolic function independent of blood pressure reduction in a transgenic model of RAAS overexpression.American journal of physiology. Heart and circulatory physiology · 2011Article
- Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease.Journal of molecular medicine (Berlin, Germany) · 2010Review
- Reactive oxygen species, NADPH oxidases, and hypertension.Hypertension (Dallas, Tex. : 1979) · 2010Article
- Aortic cell apoptosis in rat primary aldosteronism model.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2010Article
- Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension.Annals of internal medicine · 2009Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Emerging 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 serine(473) phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine(136) 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.
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Registered trials
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