Bradykinin Protects Against Oxidative Stress-Induced Endothelial Cell Senescence

H Oeseburg, D Iusuf, P van der Harst, WH van Gilst, RH Henning, Anton Roks

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Abstract

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 mu mol/L of H2O2 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 H2O2 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 H2O2-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. (Hypertension. 2009; 53[part 2]: 417-422.)
Original languageUndefined/Unknown
Pages (from-to)417-422
Number of pages6
JournalHypertension
Volume53
Issue number2
Publication statusPublished - 2009

Research programs

  • EMC COEUR-09

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