Aldosterone: A Mediator of Myocardial Necrosis and Renal Arteriopathy

Rocha, Ricardo

doi:10.1210/en.141.10.3871

Cited by 262 publications

(275 citation statements)

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“…Our laboratory has previously shown that a chronic HS diet in WT mice or in rats is not associated with cardiac tissue damage (21,26,30,37). We hypothesized that Cav-1 deficiency during the HS diet may affect eNOS expression and/or activity, not only in the blood vessels, but also in the heart.…”

Section: Discussionmentioning

confidence: 95%

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Pojoga

Yao²,

Sinha³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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RA. Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice. Am J Physiol Heart Circ Physiol 294: H1258-H1265, 2008. First published January 4, 2008 doi:10.1152/ajpheart.01014.2007.-Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1 Ϫ/Ϫ ) and wild-type control mice (WT; Cav-1 ϩ/ϩ ) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with N G -nitro-L-arginine methyl ester and more so in Cav-1 Ϫ/Ϫ than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1 Ϫ/Ϫ (maximum 0.25 Ϯ 0.06 g/mg) compared with WT (0.75 Ϯ 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1 Ϫ/Ϫ (0.27 Ϯ 0.05 g/mg) compared with WT mice (0.53 Ϯ 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10 Ϫ5 M) caused aortic relaxation in WT mice on HS (23.6 Ϯ 3.5%) and LS (23.7 Ϯ 5.5%) that was enhanced in Cav-1 Ϫ/Ϫ HS (72.6 Ϯ 6.1%) and more so in Cav-1 Ϫ/Ϫ LS mice (93.6 Ϯ 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1 Ϫ/Ϫ compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake. endothelium; nitric oxide; vascular smooth muscle; blood pressure; hypertension HIGH-SALT (HS) DIET IS OFTEN associated with increased vascular volume (4, 15). The volume overload triggers suppression of the renin-angiotensin-aldosterone system, leading to increased salt and water excretion and restoration of v...

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Section: Discussionmentioning

confidence: 95%

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Pojoga

Yao²,

Sinha³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…[1][2][3][4][5] Both the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study (EPHESUS) found that mortality, risk of hospitalization and the onset of cardiovascular events decreased significantly after adding the administration of mineralocorticoid receptor (MR) antagonist, spironolactone or eplerenone, in patients with severe heart failure, and following acute myocardial infarction complicated with left ventricular dysfunction. 6,7 These studies have had a major impact in this field, and have contributed to a rapid increase in the volume of MR antagonist prescribed for treating heart failure.…”

Section: Introductionmentioning

confidence: 99%

Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese patients with essential hypertension

Sato

Fukuda

2009

J Hum Hypertens

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“…Independent of aldosterone, patients with CKD are known to have inhibitors of NO in their serum 27 and NO synthase inhibition results in increased aldosterone secretion. 28 Finally, patients with metabolic syndrome have demonstrated adipose-mediated aldosterone excess. 29 Taken together, these data suggest that CKD increases aldosterone levels and aldosterone in turn promotes hypertension through pleiotropic mechanisms.…”

Section: Volume Expansionmentioning

confidence: 99%

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

Vemulapalli

Tyson

Svetkey

2014

Advances in Chronic Kidney Disease

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To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

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Aldosterone: A Mediator of Myocardial Necrosis and Renal Arteriopathy

Cited by 262 publications

References 0 publications

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese patients with essential hypertension

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

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