Cross talk between corticosteroids and alpha-adrenergic signalling augments cardiomyocyte hypertrophy: A possible role for SGK1

Lister, Kerrie; Autelitano, Dominic J.; Jenkins, Anna; Hannan, Ross D.; Sheppard, Karen E.

doi:10.1016/j.cardiores.2006.02.010

Cited by 61 publications

(49 citation statements)

References 62 publications

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“…SGK1 mRNA and protein abundance were measured as functional readouts of MR activation, which could be implicated in heart hypertrophy. 15,17,35 We observed a dramatic increment in SGK1 expression in the uremic LV. Spironolactone attenuated LV SGK1 upregulation, supporting the hypothesis of heart MR activation in uremic rats.…”

Section: Discussionmentioning

confidence: 62%

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

et al. 2008

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Abstract-Chronic renal failure causes left ventricular hypertrophy, but the molecular mechanisms involved remain unknown. We, therefore, investigated whether the mineralocorticoid receptor is implicated in the cardiac hypertrophy observed in uremic rats and whether mineralocorticoid receptor blockade could be protective in chronic renal failure. Experimental groups were: control rats, uremic rats (NPX) with 5/6 nephrectomy (5 weeks), and NPX rats fed with spironolactone for 5 weeks. Systolic blood pressure was increased in both NPX rats and NPX rats fed with spironolactone for 5 weeks. Echocardiography revealed concentric left ventricular hypertrophy in uremia, which was attenuated by spironolactone. Enlarged cardiomyocyte size was observed in both left and right ventricles of NPX rats, an effect that was prevented by spironolactone. Mineralocorticoid receptor antagonism attenuated the increase of ventricular brain natriuretic peptide mRNA levels induced by nephrectomy. Left ventricular gene expressions of aldosterone synthase, mineralocorticoid receptor, and hydroxysteroid dehydrogenase type 2 were the same in the 3 groups, whereas gene expression of the glucocorticoid receptor was significantly diminished in chronic renal failure rats. No significant differences in cardiac aldosterone were observed between control rats and NPX rats, although NPX rats fed with spironolactone for 5 weeks showed increased plasma aldosterone levels. However, a significant increase in serum and glucocorticoid-inducible kinase-1 mRNA expression and protein was present in the NPX group; spironolactone treatment significantly reduced serum and glucocorticoid-inducible kinase-1 mRNA and protein in the left ventricle. Uremic rats exhibited a significant increase of superoxide production and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits expression (NOX-2, NOX-4, and p47 phox ) in the left ventricle, which was prevented by the mineralocorticoid receptor antagonist. Our findings provide evidence of the beneficial effects of spironolactone in cardiac hypertrophy and cardiac oxidative stress in chronic renal failure. (Hypertension. 2008;52:295-300.) Key Words: aldosterone Ⅲ mineralocorticoid receptor Ⅲ cardiac hypertrophy Ⅲ SGK1 Ⅲ oxidative stress Ⅲ hydroxysteroid dehydrogenase type 2

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Section: Discussionmentioning

confidence: 62%

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

et al. 2008

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“…Other investigators have found that aldosterone directly stimulates myocyte surface area (Okoshi et al 2004) and remodeling of myocyte membrane (Kliche et al 2006) in cultures of neonatal myocytes, an effect presumed to be mediated by MR in the myocytes. Cortisol also increases expression of atrial natriuretic peptide in cultured neonatal myocytes, and both cortisol and aldosterone potentiate the effect of phenylephrine on hypertrophy in these cultures (Lister et al 2006), also indicating an intracardiac action at MR in these cultures.…”

Section: Role Of Mr and Gr In The Heartmentioning

confidence: 71%

Cardiac corticosteroid receptors mediate the enlargement of the ovine fetal heart induced by chronic increases in maternal cortisol

Reini¹,

Dutta²,

Wood³

et al. 2008

Journal of Endocrinology

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Previous studies have demonstrated that modest, physiologically relevant increases in maternal cortisol in late gestation result in enlargement of the fetal heart. In this study, we investigated the role of mineralocorticoid receptor (MR) or glucocorticoid receptor (GR) in this enlargement. Ewes with single fetuses were randomly assigned at w120 days of gestation to one of four groups: maternal cortisol infusion (1 mg/kg per day, cortisol); maternal cortisol infusion with fetal intrapericardial infusion of the MR antagonist (MRa) potassium canrenoate (600 mg/day; cortisolCMRa); maternal cortisol infusion with fetal intrapericardial infusion of the GR antagonist (GRa) mifepristone (50 mg/day, cortisolCGRa); and maternal saline infusion (control). At w130 days of gestation, fetal heart to body weight ratio and right ventricular (RV) and left ventricular (LV) free wall thicknesses were increased in the cortisol group when compared with control group. Fetal hearts from the cortisolCMRa group weighed significantly less, with thinner LV, RV, and interventricular septum walls, when compared with the cortisol group. Fetal hearts from the cortisolCGRa group had significantly thinner RV walls than the cortisol group. Fetal arterial pressure and heart rate were not different among groups at 130 days. Picrosirius red staining of fetal hearts indicated that the increased size was not accompanied by cardiac fibrosis. These results suggest that physiologic increases in maternal cortisol in late gestation induce fetal cardiac enlargement via MR and, to a lesser extent, by GR, and indicate that the enlargement is not secondary to an increase in fetal blood pressure or an increase in fibrosis within the fetal heart.

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“…Several previous reports have demonstrated that expression of MR mRNA was significantly increased under pathological conditions, such as post-MI and heart failure (47,48). Indeed, in vitro studies have shown that aldosterone and α-adrenergic stimulation each significantly increases the expression of MR mRNA (49,50). Since the production of aldosterone and sympathetic nerve activity in cardiac tissues are enhanced under pathological conditions particularly after MI, it is reasonable to consider that these factors raise the expression of MR in cardiac tissue.…”

Section: Discussionmentioning

confidence: 98%

Spironolactone Modulates Expressions of Cardiac Mineralocorticoid Receptor and 11.BETA.-Hydroxysteroid Dehydrogenase 2 and Prevents Ventricular Remodeling in Post-Infarct Rat Hearts

et al. 2007

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Cross talk between corticosteroids and alpha-adrenergic signalling augments cardiomyocyte hypertrophy: A possible role for SGK1

Cited by 61 publications

References 62 publications

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

Cardiac corticosteroid receptors mediate the enlargement of the ovine fetal heart induced by chronic increases in maternal cortisol

Spironolactone Modulates Expressions of Cardiac Mineralocorticoid Receptor and 11.BETA.-Hydroxysteroid Dehydrogenase 2 and Prevents Ventricular Remodeling in Post-Infarct Rat Hearts

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