Mineralocorticoid exposure and receptor activity modulate microvascular endothelial function in African Americans with and without hypertension

Mohandas, Appesh; Suboc, Tisha B; Wang, Jingli; Rong, Yuluo; Tarima, Sergey; Dharmashankar, Kodlipet; Malik, Mobin; Widlansky, Michael E.

doi:10.1177/1358863x15584753

Cited by 11 publications

(8 citation statements)

References 36 publications

(71 reference statements)

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“…Furthermore, aldosterone impairs endothelial function in normal resistance vessels, whilst aldosterone can reverse hypertension-related endothelial dysfunction in arterioles 148 . Similar benefits have been observed with eplerenone which reduces vascular stiffness, collagen/elastin ratio, pro-inflammatory mediators and systemic inflammatory markers in patients with hypertension.…”

Section: Mineralocorticoid Receptor Antagonistsmentioning

confidence: 99%

Drug Treatment of Hypertension: Focus on Vascular Health

Cameron

Lang

Touyz

2016

Drugs

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Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure elevation, the vascular system is particularly important, because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high blood pressure have greater efficacy for reducing cardiovascular risk than drugs that reduce blood pressure but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme Key Points• Hypertension is characterized by a vascular phenotype of endothelial dysfunction and structural remodeling.• Anti-hypertensive drugs that target the vascular changes associated with hypertension appear to be most efficacious• New anti-hypertensive drugs should promote vascular health as well as reducing blood pressure 3

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Section: Mineralocorticoid Receptor Antagonistsmentioning

confidence: 99%

Drug Treatment of Hypertension: Focus on Vascular Health

Cameron

Lang

Touyz

2016

Drugs

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“…Hypertensive African-Americans had impaired endothelial function, as measured by pulse arterial tonography and by ex vivo studies of adipose vessels, which was improved with spironolactone treatment. Conversely, normotensive subjects had impaired endothelial function after Aldo administration, which was also prevented by spironolactone ( 17 ). Hypertensive subjects had an associated decrease in arteriolar glucose-6-phosphate dehydrogenase (G6PD) activity compared to non-hypertensives.…”

Section: Mr In the Vascular Endothelium Contributes To Endothelial Cementioning

confidence: 99%

Mineralocorticoid Receptors in the Pathophysiology of Vascular Inflammation and Atherosclerosis

Moss

Jaffe

2015

Front. Endocrinol.

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Atherosclerosis is a chronic inflammatory disease of the vasculature that causes significant morbidity and mortality from myocardial infarction, stroke, and peripheral vascular disease. Landmark clinical trials revealed that mineralocorticoid receptor (MR) antagonists improve outcomes in cardiovascular patients. Conversely, enhanced MR activation by the hormone aldosterone is associated with increased risk of MI, stroke, and cardiovascular death. This review summarizes recent advances in our understanding of the role of aldosterone and the MR in the pathogenesis of vascular inflammation and atherosclerosis as it proceeds from risk factor-induced endothelial dysfunction and inflammation to plaque formation, progression, and ultimately rupture with thrombosis, the cause of acute ischemia. The role of the MR in converting cardiac risk factors into endothelial dysfunction, in enhancing leukocyte adhesion and infiltration into the vasculature, in promoting systemic inflammation and vascular oxidative stress, and in plaque destabilization and thrombosis are discussed. A greater understanding of the mechanisms by which the MR promotes atherosclerosis has substantial potential to identify novel treatment targets to improve cardiovascular health and decrease mortality.

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“…In contrast to the protective role of MR activation in brachial artery FMD observed in previous studies of healthy populations [18*,36], normotensive African-Americans developed endothelial microvascular dysfunction (evaluated by digital pulse arterial tonometry) in response to acute aldosterone administration and this was prevented by spironolactone[37*]. It was suggested that the endothelial dysfunction in healthy African-Americans may be due to decreased vascular G6PD activity in this population.…”

Section: Introductionmentioning

confidence: 69%

The endothelial mineralocorticoid receptor

Davel¹,

Anwar²,

Jaffe³

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review Endothelial dysfunction is an early feature of vascular disease induced by cardiovascular risk factors (CRF). In growing populations with obesity, diabetes, hypertension and heart failure, mineralocorticoid receptor (MR) antagonism improves endothelial function. This review summarizes recent advances in our understanding of the specific role of endothelial cell (EC) MR in vascular function in health and disease. Recent findings Using transgenic mice with MR expression specifically modulated in ECs, recent studies support the emerging concept that while EC-MR may be protective in health, in the presence of CRFs, EC-MR contributes to endothelial dysfunction and progression of vascular disease. Proposed mechanisms include a role for EC-MR in decreased nitric oxide production and bioavailability, increased vascular oxidative stress, regulation of epithelial sodium channels that enhance vascular stiffness, and increased EC adhesion molecules promoting inflammation. The role of EC-MR may also depend on the sex, race, or vascular bed involved. Summary Recent advances support the idea that EC-MR is a mediator of the switch from vascular health to disease in response to CRFs. Further investigation of the molecular mechanism is underway to identify therapeutic interventions that will limit the detrimental effects of EC-MR in patients at cardiovascular risk.

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Mineralocorticoid exposure and receptor activity modulate microvascular endothelial function in African Americans with and without hypertension

Cited by 11 publications

References 36 publications

Drug Treatment of Hypertension: Focus on Vascular Health

Drug Treatment of Hypertension: Focus on Vascular Health

Mineralocorticoid Receptors in the Pathophysiology of Vascular Inflammation and Atherosclerosis

The endothelial mineralocorticoid receptor

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