Oxidative DNA Damage in Kidneys and Heart of XXXX @entity19 Is Prevented by Blocking Angiotensin II and @entity1369 Receptors.

@entity11933 @entity1369 @entity101 @entity10182 @entity19 @entity26 @entity14292 @entity1564 @entity11502
INTRODUCTION: Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin- @entity1369 -system, causes the formation of reactive @entity26 species and DNA damage in kidneys and hearts of @entity101 @entity19 . To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin- @entity1369 -system on angiotensin II-induced genomic damage were studied. METHODS: In C57BL/6- @entity19 , @entity101 was induced by infusion of 600 ng/kg     min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker @entity1564 , the mineralocorticoid receptor blocker @entity14292 and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis. RESULTS: Administration of angiotensin II led to a significant increase of blood pressure, decreased only by @entity1564 . In kidneys and hearts of angiotensin II-treated animals, significant oxidative stress could be detected (1.5-fold over control). The redox-sensitive transcription factors @entity10182 and NF-kB were activated in the kidney by angiotensin II-treatment (4- and 3-fold over control, respectively) and reduced by all interventions. In kidneys and hearts an increase of DNA damage (3- and 2-fold over control, respectively) and of DNA repair (3-fold over control) was found. These effects were ameliorated by all interventions in both organs. Consistently, @entity1564 and @entity11933 were more effective than @entity14292 . CONCLUSION: @entity11502 -induced DNA damage is caused by angiotensin II type 1 receptor-mediated formation of oxidative stress in vivo. The angiotensin II-mediated physiological increase of @entity1369 adds to the DNA-damaging effects. Blocking angiotensin II and mineralocorticoid receptors therefore has beneficial effects on end-organ damage independent of blood pressure normalization.
