Bradykinin Protects Against Oxidative Stress–Induced Endothelial Cell Senescence
- 1 February 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 53 (2), 417-422
- https://doi.org/10.1161/hypertensionaha.108.123729
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 μmol/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 ω -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.Keywords
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