Resveratrol attenuates angiotensin II-induced senescence of vascular smooth muscle cells

Regul Pept. 2012 Aug 20;177(1-3):35-9. doi: 10.1016/j.regpep.2012.04.005. Epub 2012 May 2.

Abstract

Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol abundant in red wine, is known to extend the life span of diverse species. On the contrary, it was reported that angiotensin (Ang) II enhances senescence of vascular smooth muscle cells (VSMCs). We, therefore, examined whether resveratrol attenuates Ang II-induced senescence of VSMC. Senescence-associated β-galactosidase (SA β-gal) assay showed that Ang II induced senescence of VSMC. The Ang II-induced senescence was inhibited by losartan, an Ang II type 1 receptor (AT1R) antagonist but not by PD123319, Ang II type 2 receptor antagonist, indicating that AT1R is responsible for the induction of senescence. Resveratrol suppressed Ang II-induced senescence of VSMC in a dose-dependent manner. In addition, resveratrol suppressed Ang II-induced induction of p53 and its downstream target gene p21, both of which play an important role in the induction of senescence. Resveratrol suppressed senescence of VSMC possibly through inhibition of AT1R-dependent induction of p53/p21. Suppression of p53 induction may be involved in the longevity by resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / adverse effects*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Blotting, Western
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Assays
  • Imidazoles / pharmacology
  • Losartan / pharmacology
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Oxidative Stress
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism
  • beta-Galactosidase / pharmacology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Cyclin-Dependent Kinase Inhibitor p21
  • Imidazoles
  • Pyridines
  • Receptor, Angiotensin, Type 1
  • Stilbenes
  • Tumor Suppressor Protein p53
  • Angiotensin II
  • PD 123319
  • beta-Galactosidase
  • Losartan
  • Resveratrol