Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo

Nina Queisser, Kerstin Amann, Valentin Hey, Samy L. Habib, Nicole Schupp

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Epidemiological studies found an increased kidney cancer risk in hypertensive patients. These patients frequently present an increase in the mineralocorticoid aldosterone (Ald) due to a stimulated renin angiotensin aldosterone system (RAAS). Recently, we showed pro-oxidative and genotoxic effects of Ald in vitro. Here, we investigated the influence of blood pressure on aldosterone-induced oxidative damage. To distinguish whether effects in Sprague-Dawley rats treated with Ald were caused by Ald or by increased blood pressure, the mineralocorticoid receptor (MR) antagonist spironolactone was administered in a subtherapeutical dose, not lowering the blood pressure, and hydralazine, a RAAS-independent vasodilator, was given to normalize the pressure. With the antioxidant tempol, oxidative stress-dependent effects were demonstrated. Ald treatment caused kidney damage and oxidative and nitrative stress. Structural DNA damage and the mutagenic oxidative base modification 7,8-dihydro-8-oxoguanine were increased, as well as DNA repair activity and nuclear NF-κB translocation. Spironolactone and tempol decreased all markers significantly, whereas hydralazine had just slight effects. These data comprise the first report of essentially blood pressure-independent tissue- and DNA-damaging effects of Ald. A fully activated MR and the production of reactive oxygen and nitrogen species were crucial for these effects.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalFree Radical Biology and Medicine
Volume54
DOIs
StatePublished - Jan 1 2013

Keywords

  • 8-OxodG
  • Aldosterone
  • Free radicals
  • Hypertension
  • Kidney disease
  • Mineralocorticoid receptor
  • NF-κB

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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