Aldosterone directly stimulates cardiac myocyte hypertrophy

Marina P. Okoshi, Xinhua Yan, Katashi Okoshi, Masaharu Nakayama, Adam J T Schuldt, Timothy D. O'Connell, Paul C. Simpson, Beverly H. Lorell

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66 Scopus citations

Abstract

Background Clinical and experimental studies suggest that aldosterone modulates myocardial hypertrophy. From in vivo studies, it is not possible to distinguish between direct actions on myocyte growth and effects of mechanical load. In this study we tested the hypothesis that aldosterone induces myocyte hypertrophy in low-density, serum-free cultures of neonatal rat ventricular myocytes. Methods and results Hypertrophy was quantified by [ 14C]-phenylalanine incorporation and confocal microscopic assessment of myocyte surface area. Aldosterone caused a 27% increase in protein incorporation (EC 50 = 40 nmol/L) and a 29% increase in myocyte surface area compared with the vehicle control. This response was associated with increased mRNA levels of atrial natriuretic factor, α- and β-myosin heavy chain measured by RNase protection assay, and it was suppressed by the mineralocorticoid receptor blocker spironolactone. Analysis of early signaling events showed that aldosterone stimulation acutely translocated protein kinase C (PKC)-α to the membrane fraction and increased the levels of phosphorylated ERK1/2 and JNK. PD 98059, an inhibitor of the ERK activator MEK (mitogen-activated protein kinase kinase) and bisindolylmaleimide I, an inhibitor of PKC activation, each blocked aldosterone-stimulated hypertrophy. Conclusion Aldosterone directly stimulates hypertrophy in neonatal rat ventricular myocytes. The growth response is dependent on the mineralocorticoid receptor and is associated with activation of ERK, JNK, and PKC-α.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalJournal of cardiac failure
Volume10
Issue number6
DOIs
StatePublished - Dec 1 2004

Keywords

  • MAPK cascade
  • PKC pathway
  • Rat
  • cardiomyocyte
  • culture

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    Okoshi, M. P., Yan, X., Okoshi, K., Nakayama, M., Schuldt, A. J. T., O'Connell, T. D., Simpson, P. C., & Lorell, B. H. (2004). Aldosterone directly stimulates cardiac myocyte hypertrophy. Journal of cardiac failure, 10(6), 511-518. https://doi.org/10.1016/j.cardfail.2004.03.002