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

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 (10 mg/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.