Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and prevents oxidative stress in uremic rats.

Luis Michea, Andrea Villagrán, Alvaro Urzúa, Sonia Kuntsmann, Patricio Venegas, Loreto Carrasco, Magdalena Gonzalez, Elisa T. Marusic*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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 on 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 signficant increase in serum and glucocorticoid-inducible kinase-1 mRNA expression and protein was present in the NPX group; spironolactone treatment significantly reduced serum and glucocortinoid-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 p47phox) 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.

Original languageEnglish
Pages (from-to)295-300
Number of pages6
Issue number2
StatePublished - Aug 2008
Externally publishedYes


  • Aldosterone
  • Cardiac hypertrophy
  • Hydroxysteroid dehydrogenase type 2
  • Mineralocorticoid receptor
  • Oxidative stress
  • SGK1


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