The role of AT1-receptor blockade on reactive oxygen species and cardiac autonomic drive in experimental hyperthyroidism

Auton Neurosci. 2013 Oct;177(2):163-9. doi: 10.1016/j.autneu.2013.04.003. Epub 2013 Apr 26.

Abstract

The objective of this study was to explore the influence of the renin-angiotensin system on cardiac prooxidants and antioxidants levels and its association to autonomic imbalance induced by hyperthyroidism. Male Wistar rats were divided into four groups: control, losartan (10mg/kg/day by gavage, 28 day), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4+losartan. Spectral analysis (autonomic balance), angiotensin II receptor (AT1R), NADPH oxidase, Nrf2 and heme-oxygenase-1 (HO-1) myocardial protein expression, and hydrogen peroxide (H2O2) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~770%) was attenuated in the T4+losartan group (~32%) (P<0.05). AT1R, NADPH oxidase, H2O2, as well as concentration, Nrf2 and HO-1 protein expression were elevated (~172%, 43%, 40%, 133%, and 154%, respectively) in T4 group (P<0.05). H2O2 and HO-1 levels were returned to control values in the T4+losartan group (P<0.05). The overall results demonstrate a positive impact of RAS blockade in the autonomic control of heart rate, which was associated with an attenuation of H2O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism.

Keywords: Autonomic balance; Heme-oxygenase-1; Hydrogen peroxide; Hyperthyroidism; Nrf2; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Animals
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Hyperthyroidism / drug therapy
  • Hyperthyroidism / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Receptor, Angiotensin, Type 1 / physiology*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Reactive Oxygen Species
  • Receptor, Angiotensin, Type 1