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

Bradykinin protects against oxidative stress-induced endothelial cell senescence.

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1
Department of Experimental Cardiology, AB 43, University Medical Center Groningen, Antonius Deusinglaan 1, Building 3211, 9713 AV Groningen, The Netherlands. h.oeseburg@thorax.umcg.nl

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 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.

[Indexed for MEDLINE]

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