title: The role of AT1-receptor blockade on reactive oxygen species and cardiac autonomic drive in experimental hyperthyroidism.
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.
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
authors.forename: D
authors.initials: D
authors.lastname: Baraldi
authors.forename: K
authors.initials: K
authors.lastname: Casali
authors.forename: R O
authors.initials: RO
authors.lastname: Fernandes
authors.forename: C
authors.initials: C
authors.lastname: Campos
authors.forename: C
authors.initials: C
authors.lastname: Sartório
authors.forename: A
authors.initials: A
authors.lastname: Conzatti
authors.forename: G K
authors.initials: GK
authors.lastname: Couto
authors.forename: P C
authors.initials: PC
authors.lastname: Schenkel
authors.forename: A
authors.initials: A
authors.lastname: Belló-Klein
authors.forename: A R S
authors.initials: AR
authors.lastname: Araujo
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006980:Hyperthyroidism / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1
keywords: Autonomic balance; Heme-oxygenase-1; Hydrogen peroxide; Hyperthyroidism; Nrf2; ROS