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

• Published in: Autonomic neuroscience Vol. 177; no. 2; pp. 163 - 169
• Main Authors: Baraldi, D, Casali, K, Fernandes, R.O, Campos, C, Sartório, C, Conzatti, A, Couto, G.K, Schenkel, P.C, Belló-Klein, A, Araujo, A.R.S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2013
• Subjects: Advanced Basic Science; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Autonomic balance; Heart Rate - drug effects; Heart Rate - physiology; Heme-oxygenase-1; Hydrogen peroxide; Hyperthyroidism; Hyperthyroidism - drug therapy; Hyperthyroidism - metabolism; Male; Medical Education; Nrf2; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptor, Angiotensin, Type 1 - physiology; ROS; Autonomic balance; Hydrogen peroxide; Nrf2; Hyperthyroidism; ROS; Heme-oxygenase-1
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2013.04.003

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 (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 (H2 O2 ) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~ 770%) was attenuated in the T4 + losartan group (~ 32%) (P < 0.05). AT1R, NADPH oxidase, H2 O2 , 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). H2 O2 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 H2 O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism.