Bradykinin protects against oxidative stress-induced endothelial cell senescence

Hypertension. 2009 Feb;53(2):417-22. doi: 10.1161/HYPERTENSIONAHA.108.123729. Epub 2008 Dec 15.


Premature aging (senescence) of endothelial cells might play an important role in the development and progression of hypertension and atherosclerosis. We hypothesized that bradykinin, a hormone that mediates vasoprotective effects of angiotensin-converting enzyme inhibitors, protects endothelial cells from oxidative stress-induced senescence. Bradykinin treatment (0.001 to 1 nmol/L) dose-dependently decreased senescence induced by 25 micromol/L of H(2)O(2) in cultured bovine aortic endothelial cells, as witnessed by a complete inhibition of increased senescent cell numbers and a 34% reduction of the levels of the senescence-associated cell cycle protein p21. Because H(2)O(2) induces senescence through superoxide-induced DNA damage, single-cell DNA damage was measured by comet assay. Bradykinin reduced DNA damage to control levels. The protective effect of bradykinin also resulted in a significant increase in the migration of H(2)O(2)-treated bovine aorta endothelial cells in an in vitro endothelial injury model, or "scratch" assay. The protective effect of bradykinin was abolished by the bradykinin B2 receptor antagonist HOE-140 and the NO production inhibitor N(omega)-methyl-L-arginine acetate salt. Therefore, we conclude that bradykinin protects endothelial cells from superoxide-induced senescence through bradykinin B2 receptor- and NO-mediated inhibition of DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology*
  • Bradykinin B2 Receptor Antagonists
  • Cattle
  • Cell Movement / drug effects
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Receptor, Bradykinin B2 / metabolism
  • Vasodilator Agents / pharmacology*


  • Adrenergic beta-Antagonists
  • Bradykinin B2 Receptor Antagonists
  • Cyclin-Dependent Kinase Inhibitor p21
  • Reactive Oxygen Species
  • Receptor, Bradykinin B2
  • Vasodilator Agents
  • Nitric Oxide
  • icatibant
  • Bradykinin