ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Mineralocorticoid receptor blockade improves diastolic function independent of blood pressure reduction in a transgenic model of RAAS overexpression.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness.Cardiovascular diabetology · 2021Article
- Left ventricular remodeling and dysfunction in primary aldosteronism.Journal of human hypertension · 2021Review
- Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism.Frontiers in cardiovascular medicine · 2021Review
- Targeting the renin-angiotensin-aldosterone system in fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in HypertensiveFrontiers in pharmacology · 2019Article
- Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease.International journal of molecular sciences · 2018Review
- TRAF3IP2 mediates TWEAK/TWEAKR-induced pro-fibrotic responses in cultured cardiac fibroblasts and the heart.Journal of molecular and cellular cardiology · 2018Article
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- Review on Chamber-Specific Differences in Right and Left Heart Reactive Oxygen Species Handling.Frontiers in physiology · 2018Article
- Role of mineralocorticoid receptor activation in cardiac diastolic dysfunction.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.International journal of molecular sciences · 2016Review
- Low-Dose Mineralocorticoid Receptor Blockade Prevents Western Diet-Induced Arterial Stiffening in Female Mice.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice.American journal of physiology. Heart and circulatory physiology · 2015Article
- Variable transcriptional regulation of the human aldosterone synthase gene causes salt-dependent high blood pressure in transgenic mice.Circulation. Cardiovascular genetics · 2015Article
- Treatment of Primary Aldosteronism and Organ Protection.International journal of endocrinology · 2015Review
- Current perspectives on systemic hypertension in heart failure with preserved ejection fraction.Current cardiology reports · 2014Review
- Role of estrogen in diastolic dysfunction.American journal of physiology. Heart and circulatory physiology · 2014Review
- Effects of low-dose spironolactone combined with irbesartan on cardiac hypertrophy induced by pressure overload in rats.American journal of translational research · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
There is emerging evidence that aldosterone can promote diastolic dysfunction and cardiac fibrosis independent of blood pressure effects, perhaps through increased oxidative stress and inflammation. Accordingly, this investigation was designed to ascertain if mineralocorticoid receptor blockade improves diastolic dysfunction independently of changes in blood pressure through actions on myocardial oxidative stress and fibrosis. We used young transgenic (mRen2)27 [TG(mRen2)27] rats with increases in both tissue ANG II and circulating aldosterone, which manifests age-related increases in hypertension and cardiac dysfunction. Male TG(mRen2)27 and age-matched Sprague-Dawley rats were treated with either a low dose (∼1 mg·kg(-1)·day(-1)) or a vasodilatory, conventional dose (∼30 mg·kg(-1)·day(-1)) of spironolactone or placebo for 3 wk. TG(mRen2)27 rats displayed increases in systolic blood pressure and plasma aldosterone levels as well as impairments in left ventricular diastolic relaxation without changes in systolic function on cine MRI. TG(mRen2)27 hearts also displayed hypertrophy (left ventricular weight, cardiomyoctye hypertrophy, and septal wall thickness) as well as fibrosis (interstitial and perivascular). There were increases in oxidative stress in TG(mRen2)27 hearts, as evidenced by increases in NADPH oxidase activity and subunits as well as ROS formation. Low-dose spironolactone had no effect on systolic blood pressure but improved diastolic dysfunction comparable to a conventional dose. Both doses of spironolactone caused comparable reductions in ROS/3-nitrotryosine immunostaining and perivascular and interstitial fibrosis. These data support the notion mineralocorticoid receptor blockade improves diastolic dysfunction through improvements in oxidative stress and fibrosis independent of changes in systolic blood pressure.
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Registered trials
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