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 journalArticle

17 Citations (Scopus)

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 2013

Fingerprint

Oxidative stress
Blood pressure
Aldosterone
DNA Damage
Oxidative Stress
Blood Pressure
DNA
Hydralazine
Spironolactone
Renin-Angiotensin System
Angiotensins
Renin
Mineralocorticoid Receptor Antagonists
Reactive Nitrogen Species
Mineralocorticoid Receptors
Mineralocorticoids
Kidney Neoplasms
Vasodilator Agents
DNA Repair
Sprague Dawley Rats

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo. / Queisser, Nina; Amann, Kerstin; Hey, Valentin; Habib, Samy L; Schupp, Nicole.

In: Free Radical Biology and Medicine, Vol. 54, 01.2013, p. 17-25.

Research output: Contribution to journalArticle

Queisser, Nina ; Amann, Kerstin ; Hey, Valentin ; Habib, Samy L ; Schupp, Nicole. / Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo. In: Free Radical Biology and Medicine. 2013 ; Vol. 54. pp. 17-25.
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