Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodeling

Hypertens Res. 2008 Jul;31(7):1407-13. doi: 10.1291/hypres.31.1407.

Abstract

There is increasing evidence supporting potential roles of aldosterone in the pathogenesis of vascular injury. The present study aimed to determine the involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell (VSMC) remodeling. In cultured rat VSMC, the effects of aldosterone on Rho-kinase activity, the reorganization of the cytoskeleton and cellular migration were examined. Aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphate target subunit-1 (MYPT1), a marker of Rho-kinase activity, and the amount of GTP-Rho with a peak at 90 min in VSMC. Aldosterone also stimulated VSMC stress fiber formation and migration. These effects of aldosterone were markedly attenuated by pretreatment with eplerenone (10 micromol/L), a selective mineralocorticoid receptor antagonist, or Y27632 (10 micromol/L), a specific Rho-kinase inhibitor. These findings indicate that Rho-kinase is involved in the pathogenesis of aldosterone-induced VSMC remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Aldosterone / toxicity*
  • Amides / pharmacology
  • Animals
  • Cell Movement / drug effects
  • Cells, Cultured
  • Male
  • Mineralocorticoid Receptor Antagonists
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / pathology
  • Phosphorylation
  • Protein Phosphatase 1 / metabolism
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • rho-Associated Kinases / physiology*

Substances

  • Actins
  • Amides
  • Mineralocorticoid Receptor Antagonists
  • Pyridines
  • Y 27632
  • Aldosterone
  • rho-Associated Kinases
  • Ppp1r12a protein, rat
  • Protein Phosphatase 1