title: Aldosterone directly stimulates cardiac myocyte hypertrophy.
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.
  
  
  RESULTS
  Hypertrophy was quantified by [(14)C]-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, alpha- and beta-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)-alpha 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.
  
  
  CONCLUSIONS
  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-alpha.
authors.affiliation: Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Okoshi
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yan
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Adam J T
authors.initials: AJ
authors.lastname: Schuldt
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Connell
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Lorell
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006984:Hypertrophy; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D018613:Microscopy, Confocal; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D005938:Glucocorticoids; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; D003907:Dexamethasone; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases