Open AccessBradykinin Protects Against Oxidative Stress–Induced Endothelial Cell Senescence
Author(s) -
Hisko Oeseburg,
Dilek Iusuf,
Pim van der Harst,
Wiek H. van Gilst,
Robert H. Henning,
Anton J.M. Roks
Publication year - 2009
Publication title -
hypertension
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.986
H-Index - 265
eISSN - 1524-4563
pISSN - 0194-911X
DOI - 10.1161/hypertensionaha.108.123729
Subject(s) - bradykinin , senescence , oxidative stress , endothelial stem cell , endocrinology , angiotensin ii , medicine , nitric oxide , dna damage , comet assay , bradykinin receptor , chemistry , biology , receptor , in vitro , biochemistry , dna
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 H2 O2 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 H2 O2 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 H2 O2 -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 inhibitorN 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.