RESUMO
Paraquat (PQT) herbicide is widely used in agricultural practices despite being highly toxic to humans. It has been proposed that PQT exposure may promote cardiorespiratory impairment. However, the physiological mechanisms involved in cardiorespiratory dysfunction following PQT exposure are poorly known. We aimed to determine the effects of PQT on ventilatory chemoreflex control, cardiac autonomic control, and cardiac function in rats. Male Sprague-Dawley rats received two injections/week of PQT (5 mg·kg-1 ip) for 4 wk. Cardiac function was assessed through echocardiography and pressure-volume loops. Ventilatory function was evaluated using whole body plethysmography. Autonomic control was indirectly evaluated by heart rate variability (HRV). Cardiac electrophysiology (EKG) and exercise capacity were also measured. Four weeks of PQT administration markedly enlarged the heart as evidenced by increases in ventricular volumes and induced cardiac diastolic dysfunction. Indeed, end-diastolic pressure was significantly higher in PQT rats compared with control (2.42 ± 0.90 vs. 4.01 ± 0.92 mmHg, PQT vs. control, P < 0.05). In addition, PQT significantly reduced both the hypercapnic and hypoxic ventilatory chemoreflex response and induced irregular breathing. Also, PQT induced autonomic imbalance and reductions in the amplitude of EKG waves. Finally, PQT administration impaired exercise capacity in rats as evidenced by a â¼2-fold decrease in times-to-fatigue compared with control rats. Our results showed that 4 wk of PQT treatment induces cardiorespiratory dysfunction in rats and suggests that repetitive exposure to PQT may induce harmful mid/long-term cardiovascular, respiratory, and cardiac consequences.NEW & NOREWORTHY Paraquat herbicide is still employed in agricultural practices in several countries. Here, we showed for the first time that 1 mo paraquat administration results in cardiac adverse remodeling, blunts ventilatory chemoreflex drive, and promotes irregular breathing at rest in previously healthy rats. In addition, paraquat exposure induced cardiac autonomic imbalance and cardiac electrophysiology alterations. Lastly, cardiac diastolic dysfunction was overt in rats following 1 mo of paraquat treatment.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Sistema Nervoso Autônomo/efeitos dos fármacos , Células Quimiorreceptoras/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Coração/inervação , Herbicidas/toxicidade , Hipertrofia Ventricular Esquerda/induzido quimicamente , Pulmão/inervação , Paraquat/toxicidade , Ventilação Pulmonar/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Células Quimiorreceptoras/metabolismo , Tolerância ao Exercício/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Ratos Sprague-Dawley , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Myxomatous mitral valve degeneration (MMVD) is the most common heart disease affecting small dogs, it reduces cardiac output resulting in compensatory adaptation of the autonomic nervous system. Chronically, it leads to reduced heart rate variability (HRV) which is an accurate marker for autonomic balance. More than two decades ago in human medicine an indicator of autonomic balance that happens after a premature ventricular beat, it was described as heart rate turbulence (HRT). In humans with ischemic heart disease, the absence of HRT has proven to be a more accurate and an independent indicator of mortality than known HRV parameters. Currently, there are very few studies of HRT in dogs and it is still not tested in small dogs within different stages of myxomatous mitral valve disease. AIM: The aim of this study was to assess the HRT indicators, onset and slope, in small dogs with myxomatous mitral valve disease and to statistically test it. METHODS: Dogs under 25 kg had electrocardiogram and echocardiography performed and, in some patients, holter monitoring was carried out. Data were divided into groups B1, B2, C, and D for mean comparison with analysis of variance and Tukey test. In addition, receiver operating characteristic (ROC) curve for differentiating among symptomatic and asymptomatic dogs and for differentiating between remodeled and non-remodeled hearts. The Pearson was executed after correlations of turbulence onset (TO) and turbulence slope (TS) with commonly used echocardiographic parameters. RESULTS: Variance analyses held significant differences in TO and TS between stages B1 from stages C and D, while B2 held similarity to the other groups. In the receiver operating curve was found a very good area under the curve for differentiating among symptomatic and asymptomatic dogs and remodeled and non-remodeled dogs. Few echocardiography parameters held weak correlation with TO while others held weak to moderate correlation with TS. CONCLUSION: In dogs with MMVD and without other diseases, HRT is a feasible indicator for autonomic balance. Our result suggests HRT changes as the MMVD progresses and congestive heart failure is present. More studies with HRT are needed. The number of ventricular premature contractions (VPCs) may be the strongest limitation for the technique.
Assuntos
Doenças do Cão , Doenças das Valvas Cardíacas , Complexos Ventriculares Prematuros , Animais , Cães , Eletrocardiografia Ambulatorial/veterinária , Frequência Cardíaca , Doenças das Valvas Cardíacas/veterinária , Humanos , Valva Mitral , Complexos Ventriculares Prematuros/veterináriaRESUMO
BACKGROUND AND AIMS: Metformin has been known to promote cardiovascular benefits in humans and animal models, even in non-diabetic subjects. However, its chronic effects on hypertension-related autonomic dysfunction remain poorly understood. Therefore, we evaluate the cardiac autonomic effects of chronic metformin in hypertensive rats. METHODS AND RESULTS: Twelve-week-old male SHR and Wistar rats were separated into 3 groups: WN (Wistar normotensive); SC (SHR hypertensive control); and SM (SHR: Metformin 300 mg/kg/day for 30 days). Spontaneous and induced (by phenylephrine and sodium nitroprusside) baroreflexes were analysed in catheterised rats. Next, cardiac autonomic tone was evaluated through heart rate shift by atropine (parasympathetic) or atenolol (sympathetic). Plasma TNFα was assessed by ELISA. Western blot analyses of inflammatory, oxidant and antioxidant proteins were performed. Cardiac parasympathetic tone and baroreflex function were lower in SC than in WN, whereas cardiac sympathetic tone was higher. Metformin treatment in non-diabetic hypertensive rats reduced the resting heart rate, attenuated the cardiac sympathetic tone and improved baroreflex (especially in the offsetting of rising BP), while blood pressure and glycaemia remained unchanged. Cardiac sympathetic tone correlated negatively with spontaneous baroreflex. Metformin reduced plasma TNFα levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2. CONCLUSION: Chronic metformin presented anti-inflammatory and antioxidant effects and, independently of alterations in glycaemia, it improved cardiac autonomic parameters that are impaired in hypertension, being related to end-organ damage and mortality. These findings open up perspectives for future innovative uses of metformin in cardiovascular diseases, especially in hypertension.
Assuntos
Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Coração/inervação , Hipertensão/tratamento farmacológico , Mediadores da Inflamação/sangue , Metformina/farmacologia , Animais , Antioxidantes/metabolismo , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Ratos Endogâmicos SHR , Ratos WistarRESUMO
The aim of this study was to compare the sleep quality, depression, anxiety, and autonomic function of a group of kidney-transplanted recipients who joined a combined exercise program (KTRt) or remained sedentary (KTRs). A total of 20 kidney-transplanted recipients, split into two groups (10 KTRt and 10 KTRs), joined the study. Heart rate variability, cardiorespiratory capacity, depression, and sleep questionnaires were evaluated. KTRt presented lower Pittsburgh Sleep Quality Index and greater entropy, and increased parasympathetic and decreased sympathetic modulation than KTRs. Anxiety level was minimal and depression was absent in both groups. KTRt group presented better sleep quality and better autonomic modulation than KTRs.
Assuntos
Ansiedade/terapia , Sistema Nervoso Autônomo , Depressão/terapia , Exercício Físico , Frequência Cardíaca , Transplante de Rim/reabilitação , Avaliação de Resultados em Cuidados de Saúde , Transtornos do Sono-Vigília/terapia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
There is currently a lack of information adjacent on the influence of sex and age in heart rate variability (HRV), adjusted according to accelerometer-based physical activity (PADL). We hypothesized that the effect of sex and age on the HRV should be reduced or absent in individuals with a suitable PADL level. We aim to evaluate the influence of sex and age on HRV, adjusted for the confounding effects of the PADL level. A total of 485 age-stratified subjects (18-39, 40-59, and ≥60 years) underwent HRV analyses at rest and 7-day assessments of accelerometer-based PADL. Multivariate analyses of covariance were done using log-transformed HRV indices as outcomes, age and sex as fixed factors, and PADL, cardiovascular risk, fat body mass, and heart rate (HR) at rest as covariates. Despite the adjustment for directly measured PADL, women had better indices of vagal tone, whereas men had higher sympathetic influence. Also, compared to middle-aged and older adults, younger individuals (ages 18-39 years) presented better HRV. Multiple regression analyses confirmed that age and sex were the main predictors of HRV indices, even after adjusting for PADL directly assessed by triaxial accelerometer and HR. We also observed that the correlation between some HRV indexes and the different indexes of physical activity directly evaluated was significant, but not very consistent. Thus, HRV indices are influenced by age and sex, regardless of accelerometer-based physical activity. Interventions with physical activity and exercise aimed at improving the autonomic modulation of asymptomatic adults should take such differences into account.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Doenças Cardiovasculares/fisiopatologia , Exercício Físico/fisiologia , Fatores Sexuais , Fatores Etários , Frequência Cardíaca/fisiologia , Fatores de Risco , AcelerometriaRESUMO
PURPOSE: Aging impairs the autonomic balance reducing the vagal and increasing the sympathetic components of heart rate variability (HRV) and this could be associated with a decline in physical capacity. Inspiratory muscle training (IMT) is a possible tool to attenuate this physical capacity decline in older women. The aim of this study was to investigate the influence of IMT in the older women on physical capacity and autonomic cardiac modulation at rest and post exercise. METHODS: 20 female participants 60-72 years old were randomly allocated in two groups. One group underwent IMT set at 50% of maximum inspiratory pressure (MIP), every day for 4 weeks (IMT-group). The placebo group performed the same training procedure but with a minimal resistance (5% MIP; PLA-group). Every week, the IMT load was readjusted and the HRV evaluated at rest. The six-minute walk test (6MWT) was performed once pre and post IMT-intervention. The IMT-group and PLA-group performed the same test and intervention procedures. RESULTS: After a 5 weeks intervention, the MIP had significantly improved in the IMT-group but not in the PLA-group (p < 0.01; es = 1.17). The high frequency power of the HRV spectrum had already improved by the second week (p < 0.01; es = 1.13) and remained elevated until the last week of intervention (p < 0.01; es = 1.43). The same positive results were described in 6MWT distance (p = 0.04; es = 0.39) and the change (∆) of heart rate recovery (HRR) from 1 min (p = 0.02; es = 0.68). CONCLUSION: IMT increases HRV, improves 6MWT distance and HRR.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Tolerância ao Exercício , Coração/fisiologia , Condicionamento Físico Humano/métodos , Músculos Respiratórios/fisiologia , Idoso , Feminino , Coração/inervação , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Condicionamento Físico Humano/efeitos adversosRESUMO
The present study has the objective of evaluating the effects of exercise training, using moderate intensity walking (60 to 80% of maximum heart rate), from 30 to 50 minutes, three times a week, in alternate days, during eight weeks, on heart rate variability in dogs with myxomatous valve disease (MVD). For that, 20 dogs in stages B1 (1), B2 (14) and C2 (5) of MVD (ACVIM classification) were divided into untrained control group (CG, n=9) and training group (TG, n=11), and assessed at baseline (T0), after four (T1) and eight weeks (T2). Only one B1 and five B2 dogs completed the training program. In the time domain, the rMSSD was greater in TG in T1 (155,5+42,07) and T2 (199,8+83,54) than CG (T1:91,17+35,79 and T2:88,17+57,51). In the frequency domain, the variable High Frequency (HF) increased in TG in T1 (30950+25810) and T2 (40300+33870) when compared to the CG (T1:19090+23210 and T2:18810+22200) and within the group TG in T2 in relation to T0 (29340+20950). The proposed walking protocol is concluded to have increased the rMSSD and HF variables in TG, representing an increase of the parasympathetic tonus, justifying the indication of this therapy in B1 and B2 stages of MVD.(AU)
O presente estudo objetivou avaliar o efeito do treinamento físico, utilizando-se a caminhada de moderada intensidade (60 a 80% da frequência cardíaca máxima), por 30 a 50 minutos, três vezes por semana, em dias alternados, durante oito semanas, sobre a variabilidade da frequência cardíaca em cães com degeneração mixomatosa valvar (DMV). Para tanto, 20 cães nos estágios B1 (1), B2 (14) e C2 (5) da DMV (classificação ACVIM) foram divididos em grupo controle não treinado (GC, n=9) e grupo treinamento (GT, n=11) e avaliados no início do estudo (T0), após quatro (T1) e oito semanas (T2). Apenas um cão B1 e cinco B2 completaram o programa de treinamento. No domínio do tempo, a variável rMSSD foi maior no GT em T1 (155,5+42,07) e T2 (199,8+83,54) que o GC (T1:91,17+35,79 e T2:88,17+57,51). No domínio da frequência, a variável High Frequency (HF) aumentou no GT em T1 (30950+25810) e T2 (40300+33870) comparada à do GC (T1:19090+23210 e T2:18810+22200), e dentro do GT no T2 em relação ao T0 (29340+20950). Dessa forma, conclui-se que o protocolo de treinamento proposto aumentou as variáveis rMSSD e HF no GT, representando aumento do tônus parassimpático, o que fundamenta a indicação dessa terapia nos estágios B1 e B2 da DMV.(AU)
Assuntos
Animais , Cães , Doenças das Valvas Cardíacas/terapia , Doenças das Valvas Cardíacas/veterinária , Condicionamento Físico Animal , Frequência Cardíaca , Endocárdio/fisiopatologia , Fibrose/veterinária , Cardiopatias/veterináriaRESUMO
The present study has the objective of evaluating the effects of exercise training, using moderate intensity walking (60 to 80% of maximum heart rate), from 30 to 50 minutes, three times a week, in alternate days, during eight weeks, on heart rate variability in dogs with myxomatous valve disease (MVD). For that, 20 dogs in stages B1 (1), B2 (14) and C2 (5) of MVD (ACVIM classification) were divided into untrained control group (CG, n=9) and training group (TG, n=11), and assessed at baseline (T0), after four (T1) and eight weeks (T2). Only one B1 and five B2 dogs completed the training program. In the time domain, the rMSSD was greater in TG in T1 (155,5+42,07) and T2 (199,8+83,54) than CG (T1:91,17+35,79 and T2:88,17+57,51). In the frequency domain, the variable High Frequency (HF) increased in TG in T1 (30950+25810) and T2 (40300+33870) when compared to the CG (T1:19090+23210 and T2:18810+22200) and within the group TG in T2 in relation to T0 (29340+20950). The proposed walking protocol is concluded to have increased the rMSSD and HF variables in TG, representing an increase of the parasympathetic tonus, justifying the indication of this therapy in B1 and B2 stages of MVD.(AU)
O presente estudo objetivou avaliar o efeito do treinamento físico, utilizando-se a caminhada de moderada intensidade (60 a 80% da frequência cardíaca máxima), por 30 a 50 minutos, três vezes por semana, em dias alternados, durante oito semanas, sobre a variabilidade da frequência cardíaca em cães com degeneração mixomatosa valvar (DMV). Para tanto, 20 cães nos estágios B1 (1), B2 (14) e C2 (5) da DMV (classificação ACVIM) foram divididos em grupo controle não treinado (GC, n=9) e grupo treinamento (GT, n=11) e avaliados no início do estudo (T0), após quatro (T1) e oito semanas (T2). Apenas um cão B1 e cinco B2 completaram o programa de treinamento. No domínio do tempo, a variável rMSSD foi maior no GT em T1 (155,5+42,07) e T2 (199,8+83,54) que o GC (T1:91,17+35,79 e T2:88,17+57,51). No domínio da frequência, a variável High Frequency (HF) aumentou no GT em T1 (30950+25810) e T2 (40300+33870) comparada à do GC (T1:19090+23210 e T2:18810+22200), e dentro do GT no T2 em relação ao T0 (29340+20950). Dessa forma, conclui-se que o protocolo de treinamento proposto aumentou as variáveis rMSSD e HF no GT, representando aumento do tônus parassimpático, o que fundamenta a indicação dessa terapia nos estágios B1 e B2 da DMV.(AU)
Assuntos
Animais , Cães , Endocárdio/fisiopatologia , Frequência Cardíaca , Doenças das Valvas Cardíacas/terapia , Doenças das Valvas Cardíacas/veterinária , Condicionamento Físico Animal , Fibrose/veterinária , Cardiopatias/veterináriaRESUMO
The association between functional ß2 adrenergic receptor (ß2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the ß2-AR gene (Gln27Glu ß2 and Arg16Gly ß2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly ß2 and Gln27Glu ß2 polymorphisms and between ß2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of ß2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals.
RESUMO
Early endothelial progenitor cells (early EPC) and late EPC are involved in endothelial repair and can rescue damaged endothelial cells by transferring organelles through tunneling nanotubes (TNT). In rodents, EPC mobilization from the bone marrow depends on sympathetic nervous system activity. Indirect evidence suggests a relation between autonomic derangements and human EPC mobilization. We aimed at testing whether hypertension-related autonomic imbalances are associated with EPC impairment. Thirty controlled-essential hypertensive patients [systolic blood pressure/diastolic blood pressure = 130(120-137)/85(61-88) mmHg; 81.8% male] and 20 healthy normotensive subjects [114(107-119)/75(64-79) mmHg; 80% male] were studied. Mononuclear cells were cultured on fibronectin- and collagen-coated dishes for early EPC and late EPC, respectively. Low (LF)- and high (HF)-frequency components of short-term heart rate variability were analyzed during a 5-min rest, an expiration/inspiration maneuver, and a Stroop color-word test. Modulations of cardiac sympathetic and parasympathetic activities were evaluated by LF/HF (%) and HF power (ms(2)), respectively. In controlled-hypertensive patients, the numbers of early EPC, early EPC that emitted TNT, late EPC, and late EPC that emitted TNT were 41, 77, 50, and 88% lower than in normotensive subjects (P < 0.008), respectively. In controlled-hypertensive patients, late EPC number was positively associated with cardiac parasympathetic reserve during the expiration/inspiration maneuver (rho = 0.45, P = 0.031) and early EPC with brachial flow-mediated dilation (rho = 0.655; P = 0.049); also, late TNT number was inversely related to cardiac sympathetic response during the stress test (rho = -0.426, P = 0.045). EPC exposure to epinephrine or norepinephrine showed negative dose-response relationships on cell adhesion to fibronectin and collagen; both catecholamines stimulated early EPC growth, but epinephrine inhibited late EPC growth. In controlled-hypertensive patients, sympathetic overactivity/parasympathetic underactivity were negatively associated with EPC, suggesting that reducing sympathetic/increasing parasympathetic activation might favor endothelial repair.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Células Endoteliais , Hipertensão/tratamento farmacológico , Nanotubos , Células-Tronco , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Adesão Celular , Comunicação Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Epinefrina/farmacologia , Feminino , Frequência Cardíaca , Humanos , Hipertensão/diagnóstico , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/farmacologia , Sistema Nervoso Parassimpático/fisiopatologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatação , Adulto JovemRESUMO
Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.
Assuntos
Coração/fisiologia , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Desmame , Fatores Etários , Animais , Dieta , Masculino , Obesidade/etiologia , Ratos , Ratos WistarRESUMO
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.