The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure

Cat, Aurélie Nguyen Dinh; Griol-Charhbili, Violaine; Loufrani, Laurent; Labat, Carlos; Benjamin, Laura E.; Farman, Nicolette; Lacolley, Patrick; Henrion, Didier; Jaisser, Frédéric

doi:10.1096/fj.09-147926

Cited by 132 publications

(54 citation statements)

References 44 publications

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“…Endothelial MR is involved in inflammatory and profibrotic responses15 and the regulation of vasomotor function 16. Although these studies showed that endothelial MR does not contribute to BP regulation, overexpression of MR in the endothelium was found to affect BP 17. MR in myeloid cells and macrophages has roles in cardiac fibrosis and DOCA/salt‐induced BP elevation 18, 19.…”

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confidence: 99%

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

Nakamura

Kurihara

Kobayashi

et al. 2018

JAHA

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BackgroundMineralocorticoid receptor (MR) has pathological roles in various cell types, including renal tubule cells, myocytes, and smooth muscle cells; however, the role of MR in intestinal epithelial cells (IECs) has not been sufficiently evaluated. The intestine is the sensing organ of ingested sodium; accordingly, intestinal MR is expected to have essential roles in blood pressure (BP) regulation.Methods and ResultsWe generated IEC‐specific MR knockout (IEC‐MR‐KO) mice. With a standard diet, fecal sodium excretion was 1.5‐fold higher in IEC‐MR‐KO mice, with markedly decreased colonic expression of β‐ and γ‐epithelial sodium channel, than in control mice. Urinary sodium excretion in IEC‐MR‐KO mice decreased by 30%, maintaining sodium balance; however, a low‐salt diet caused significant reductions in body weight and BP in IEC‐MR‐KO mice, and plasma aldosterone exhibited a compensatory increase. With a high‐salt diet, intestinal sodium absorption markedly increased to similar levels in both genotypes, without an elevation in BP. Deoxycorticosterone/salt treatment elevated BP and increased intestinal sodium absorption in both genotypes. Notably, the increase in BP was significantly smaller in IEC‐MR‐KO mice than in control mice. The addition of the MR antagonist spironolactone to deoxycorticosterone/salt treatment eliminated the differences in BP and intestinal sodium absorption between genotypes.ConclusionsIntestinal MR regulates intestinal sodium absorption in the colon and contributes to BP regulation. These regulatory effects are associated with variation in epithelial sodium channel expression. These findings suggest that intestinal MR is a new target for studying the molecular mechanism of hypertension and cardiovascular diseases.

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confidence: 99%

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

Nakamura

Kurihara

Kobayashi

et al. 2018

JAHA

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“…In contrast, overexpression of the MR in endothelial cells lead to a moderate increase in blood pressure in untreated mice. 4 We conclude that MR expression in endothelial cells at a physiological level does not significantly contribute to blood pressure regulation. However, when MR expression is upregulated during disease, [34][35][36] it might become more relevant for endothelial effects on blood pressure as demonstrated by experimental MR overexpression.…”

Section: Blood Pressure Regulationmentioning

confidence: 69%

“…However, when MR expression is upregulated during disease, [34][35][36] it might become more relevant for endothelial effects on blood pressure as demonstrated by experimental MR overexpression. 4 Which other cell types or mechanisms might be involved in the aldosterone effect on vascular reactivity and blood pressure? MR in vascular smooth muscle cells aggravates the vascular response to angiotensin II and the development of hypertension in aged mice.…”

Section: Blood Pressure Regulationmentioning

confidence: 99%

“…1 The classical action of aldosterone and the mineralocorticoid receptor (MR) in the kidney is the tubular regulation of sodium reabsorption and potassium secretion. However, the MR is not only expressed in kidney epithelial cells but also in other cell types within and outside the kidney, such as podocytes, 2 renal endothelial cells, [3][4][5] vascular smooth muscle cells, 6 immune cells, 2,7,8 the brain, 9 or the heart. 10,11 During the past 2 decades, it has been recognized that activation of the MR during disease may become maladaptive and then can directly mediate end organ damage.…”

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confidence: 99%

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Deoxycorticosterone Acetate/Salt–Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure

et al. 2016

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Abstract-Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches.Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt-induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney.

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“…where activation leads to insertion of transporters which increase sodium and water reabsorption. The receptor is also found in non-epithelial tissues such as the heart (Sainte- Marie et al 2007), the vasculature (Nguyen Dinh Cat et al 2010, McCurley et al 2012) and adipose tissue (Caprio et al 2007, Nguyen Dinh Cat et al 2011, Briones et al 2012. Interestingly, increased MR expression in adipose tissue has been observed in obesity (Hirata et al 2012, Urbanet et al 2015.…”

Section: Introductionmentioning

confidence: 99%

Adipocytes, aldosterone and obesity-related hypertension

Cat¹,

Friederich‐Persson²,

White³

et al. 2016

Journal of Molecular Endocrinology

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Aldosterone and obesity a nguyen dinh cat and others 57:1 F7-F21 AbstractUnderstanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension.

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The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure

Cited by 132 publications

References 44 publications

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

Deoxycorticosterone Acetate/Salt–Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure

Adipocytes, aldosterone and obesity-related hypertension

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