Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes

Lalevée, Nathalie; Rebsamen, Michela; Barrère-Lemaire, Stéphanie; Perrier, Emeline; Nargeot, Joël; Bénitah, Jean‐Pierre; Rossier, Michel F.

doi:10.1016/j.cardiores.2005.05.009

Cited by 113 publications

(90 citation statements)

References 49 publications

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“…Furthermore, non-genomic effects of aldosterone on I Ca,L were excluded and co-incubation with spironolactone blunted upregulation of I Ca,L , possible effects of spironolactone on the channel´s biophysical properties were not described. Similar effects of aldosterone on current density and, respectively, the missing effect on biophysical properties of I Ca,L were obtained in ventricular neonatal rat cardiomyocytes (Lalevee et al 2005). Correlation of I Ca,L current density and plasma level of aldosterone was demonstrated Briggs et al 1959 Spironolactone prolongs action potential duration in isolated rabbit atrium.…”

Section: Genomic Effects On the Ventricular Levelsupporting

confidence: 54%

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation

Laszlo¹,

Bentz²,

Schreieck³

2011

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Abstract. Atrial fibrillation (AF) is the most common sustained arrhythmia in man. Over the past years, importance of the renin-angiotensin-aldosterone system in AF pathophysiology has been recognized. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed with special regards concerning the effects on AF-induced structural remodeling. However, there is more and more evidence that MR antagonism also influences atrial electrophysiology and, respectively, AF-induced electrical remodeling, whereas the molecular mechanisms are almost unknown.The aim of this mini-review is to give an overview about the role of aldosterone in AF pathophysiology in principle and to summarize current available data concerning affection of cardiac ion channels by aldosterone and MR antagonism. Finally, as modulation of oxidative stress is discussed as one main therapy principle of "upstream" treatment of AF, potential mechanisms how modulation of oxidative stress by aldosterone and accordingly MR antagonism might alter atrial ion currents are delineated.Summarized, publications concerning potential mechanisms of aldosterone-and MR antagonismmodulated cardiac ion channels in various experimental settings are almost exclusively limited to the ventricular level and, partly, they are also contradictorily. Translation of these data to the atria is problematic because atrial and ventricular electrophysiology exhibit remarkable differences. It can be concluded that further research on the "atrial level" is needed in order to clarify the potential impact of the affection of atrial ion channels by aldosterone and accordingly MR antagonism in "upstream" therapy of AF.

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Section: Genomic Effects On the Ventricular Levelsupporting

confidence: 54%

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation

Laszlo¹,

Bentz²,

Schreieck³

2011

gpb

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“…24,[27][28][29] Therefore, targeting aldosterone synthesis and release may be clinically important in preventing cardiovascular disease. Ca 2+ ions are conveyed through the T-type Ca channel to the mitochondria, where they activate aldosterone synthesis, which in turn stimulates T-type Ca channel expression, 30,31 creating a positive feedback loop of aldosterone biosynthesis in adrenal cells. Efonidipine, another T-type CCB, has been shown to inhibit aldosterone synthesis and secretion in vitro, 9 as well as in both healthy subjects and patients with essential hypertension.…”

Section: Discussionmentioning

confidence: 99%

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

et al. 2010

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Benidipine inhibits both L-and T-type Ca channels, and has been shown to dilate the efferent arterioles as effectively as the afferent arterioles. In this study, we conducted an open-label and randomized trial to compare the effects of benidipine with those of amlodipine on blood pressure (BP), albuminuria and aldosterone concentration in hypertensive patients with mild-tomoderate stage chronic kidney disease (CKD). Patients with BPX130/80 mm Hg, with estimated glomerular filtration rate (eGFR) of 30-90 ml min À1 per 1.73 m 2 , and with albuminuria430 mg per g creatinine (Cr), despite treatment with the maximum recommended dose of angiotensin II receptor blockers (ARBs) were randomly assigned to two groups. Patients received either of the following two treatment regimens: 2 mg per day benidipine, which was increased up to a dose of 8 mg per day (n¼52), or 2.5 mg per day amlodipine, which was increased up to a dose of 10 mg per day (n¼52). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was observed in both groups. The decrease in the urinary albumin to Cr ratio in the benidipine group was significantly lower than that in the amlodipine group. Although plasma renin activity was not different in the two groups, plasma aldosterone levels were significantly decreased in the benidipine group. Moreover, urinary Na/K ratio was significantly decreased in the benidipine group but remained unchanged in the serum. It may be concluded that benidipine results in a greater reduction of plasma aldosterone and albuminuria than amlodipine, and that these effects are independent of BP reduction.

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“…73 The mechanisms underlying the generation of arrhythmias remain unclear, although it has been shown that in normal rat neonatal cardiomyocytes, aldosterone increases L-type calcium current amplitude in ventricular myocytes. 74 Aldosterone exerts opposing effects on T channel…”

Section: Aldosterone Actions In the Heartmentioning

confidence: 99%

Mechanisms of Mineralocorticoid Action

Fuller¹,

Young²

2005

Hypertension

280

169

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Abstract-Sodium transport in epithelial tissues is regulated by the physiological mineralocorticoid aldosterone. The response to aldosterone is mediated by the mineralocorticoid receptor (MR), for which the crystal structure of the ligand-binding domain has recently been established. The classical mode of action for this receptor involves the regulation of gene transcription. Several genes have now been shown to be regulated by aldosterone in epithelial tissues. Of these, the best characterized is serum-and glucocorticoid-regulated kinase, which increases sodium influx through the epithelial sodium channel. Turnover of these channels in the cell membrane is mediated by Nedd4 -2, a ubiquitin protein ligase; serum-and glucocorticoid-regulated kinase interacts with and phosphorylates Nedd4 -2, thereby rendering it unable to bind the sodium channels. Key Words: aldosterone Ⅲ sodium channels Ⅲ fibrosis T he isolation of aldosterone just over 50 years ago established it as the primary physiological mineralocorticoid. 1 Sodium transport, and hence salt balance, is regulated by a number of mechanisms; however, aldosterone has a critical role. Aldosterone exerts its effects on the distal nephron (and colon) as the last point of sodium reabsorption; it is thus the final arbiter. 2,3 The importance of aldosterone in the maintenance of sodium homeostasis is seen in a series of monogenetic causes of hypertension, 2 in Conn's syndrome, and in disorders in which mineralocorticoid action is compromised with consequent, life-threatening salt losses. 3 Although other pathophysiological consequences of aldosterone excess were identified by Selye 4 over 60 years ago, their significance has only recently been appreciated. Evidence from the Randomized ALdactone Evaluation Study (RALES) and EPlerenone neuroHormonal Efficacy and SUrvival Study (EPHESUS) trials of beneficial effects of mineralocorticoid antagonist therapy on morbidity and mortality in cardiac failure has focused attention beyond the kidney to effects of mineralocorticoids more broadly in the cardiovascular system. 5 Although an understanding of the molecular basis of aldosterone action has tended to lag behind advances in the biology of other steroid hormones, the last decade has seen significant advances toward an understanding of the mechanisms of mineralocorticoid action. The primary mediator of the response to aldosterone is the mineralocorticoid receptor (MR), the ligand-binding domain (LBD) of which has been recently crystallized. 6 -8 Although the MR primarily acts as a transcription factor, recent evidence suggests that it may also mediate nongenomic (or nonnuclear) activation of second messenger pathways. In addition, there is a growing body of evidence that some actions of aldosterone may involve a receptor other than the MR. The cellular and molecular mediators, including proteins induced by aldosterone, have been characterized in sodium transporting epithelia; however, the critical molecular events in the vasculature remain to be determined. In this brief r...

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Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes

Cited by 113 publications

References 49 publications

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

Mechanisms of Mineralocorticoid Action

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