Naringin and trimetazidine improve baroreflex sensitivity and nucleus tractus solitarius electrical activity in renal ischemia-reperfusion injury / Naringin and trimetazidine improve baroreflex sensitivity and nucleus tractus solitarius electrical activity in renal ischemia-reperfusion injury

Resumo Fundamento: O núcleo do trato solitário (NTS) é uma área do cérebro que desempenha um papel fundamental na regulação renal e cardiovascular através dos impulsos dos barorreceptores. Objetivos: O objetivo deste estudo foi avaliar o efeito da Naringina (NAR) e trimetazidina (TMZ), isoladamente e combinadas, na atividade elétrica do NTS e na sensibilidade barorreflexa (SBR) na lesão de isquemia e reperfusão (I/R) renal. Métodos: Foram utilizados quarenta ratos machos Sprague-Dawley (200-250 g), alocados em 5 grupos com 8 ratos cada. Grupos: 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; e 5) TMZ5 + NAR100. A veia femoral esquerda foi canulada para infundir a solução salina ou droga e avaliar a SBR. A I/R foi induzida por oclusão dos pedículos renais por 45 min, seguida de reperfusão de 4 horas. O eletroencefalograma local do NTS foi registrado antes, durante a isquemia e durante a reperfusão. A fenilefrina foi injetada por via intravenosa para avaliar a SBR ao final do tempo de reperfusão. Os dados foram analisados por ANOVA de duas vias com medidas repetidas seguida pelo teste post hoc de Tukey. Um valor de p<0,05 foi considerado como significativo. Resultados: As ondas elétricas do NTS não se alteraram durante o tempo de isquemia, mas diminuíram significativamente durante todos os tempos de reperfusão. A atividade elétrica do NTS e a SBR foram reduzidas drasticamente em ratos com lesão I/R; no entanto, a administração de NAR e TMZ, isoladamente e combinadas, melhorou significativamente essas alterações em ratos com lesão I/R. Conclusões: Os resultados mostraram que a lesão de I/R leva à redução da atividade elétrica da SBR e do NTS, e pode haver uma ligação entre a I/R e a diminuição da SBR. Além disso, a NAR e a TMZ são agentes promissores para tratar complicações de I/R.

Abstract Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.

Multicomponent exercise training in cardiovascular complexity in prefrail older adults: a randomized blinded clinical pilot study

The aim of this study was to investigate the effects of multicomponent training on baroreflex sensitivity (BRS) and heart rate (HR) complexity of prefrail older adults. Twenty-one prefrail community-dwelling older adults were randomized and divided into multicomponent training intervention group (MulTI) and control group (CG). MulTI performed multicomponent exercise training over 16 weeks and CG was oriented to follow their own daily activities. The RR interval (RRi) and blood pressure (BP) series were recorded for 15 min in supine and 15 min in orthostatic positions, and calculation of BRS (phase, coherence, and gain) and HR complexity (sample entropy) were performed. A linear mixed model was applied for group, assessments, and their interaction effects in supine position. The same test was used to assess the active postural maneuver and it was applied separately to each group considering assessments (baseline and post-intervention) and positions (supine and orthostatic). The significance level established was 5%. Cardiovascular control was impaired in prefrail older adults in supine position. Significant interactions were not observed between groups or assessments in terms of cardiovascular parameters. A 16-week multicomponent exercise training did not improve HR complexity or BRS in supine rest or in active postural maneuver in prefrail older adults.

Effects of exercise training on autonomic modulation and mood symptoms in patients with obstructive sleep apnea

We evaluated the effects of exercise training (ET) on the profile of mood states (POMS), heart rate variability, spontaneous baroreflex sensitivity (BRS), and sleep disturbance severity in patients with obstructive sleep apnea (OSA). Forty-four patients were randomized into 2 groups, 18 patients completed the untrained period and 16 patients completed the exercise training (ET). Beat-to-beat heart rate and blood pressure were simultaneously collected for 5 min at rest. Heart rate variability (RR interval) was assessed in time domain and frequency domain (FFT spectral analysis). BRS was analyzed with the sequence method, and POMS was analyzed across the 6 categories (tension, depression, hostility, vigor, fatigue, and confusion). ET consisted of 3 weekly sessions of aerobic exercise, local strengthening, and stretching exercises (72 sessions, achieved in 40±3.9 weeks). Baseline parameters were similar between groups. The comparisons between groups showed that the changes in apnea-hypopnea index, arousal index, and O2 desaturation in the exercise group were significantly greater than in the untrained group (P<0.05). The heart rate variability and BRS were significantly higher in the exercise group compared with the untrained group (P<0.05). ET increased peak oxygen uptake (P<0.05) and reduced POMS fatigue (P<0.05). A positive correlation (r=0.60, P<0.02) occurred between changes in the fatigue item and OSA severity. ET improved heart rate variability, BRS, fatigue, and sleep parameters in patients with OSA. These effects were associated with improved sleep parameters, fatigue, and cardiac autonomic modulation, with ET being a possible protective factor against the deleterious effects of hypoxia on these components in patients with OSA.

Influences on the Functional Behavior of Great Arteries during Orthostasis / Gravidade Influencia o Comportamento Funcional das Grandes Artérias Durante a Ortostase

Abstract Background: Arterial compliance reduction has been associated with aging and hypertension in supine position. However, the dynamic effects of orthostatism on aortic distensibility has not been defined. Objective: We sought to determine the orthostatic influence and the interference of age, blood pressure (BP) and heart rate (HR) on the great arteries during gravitational stress. Methods: Ninety-three healthy volunteers (age 42 ± 16 years). Carotid-femoral pulse wave velocity (PWV) assumed as aortic stiffness was assessed in supine position (basal phase), during tilt test (TT) (orthostatic phase) and after return to supine position (recovery phase). Simultaneously with PWV acquisition, measures of BP and HR rate were recorded. Results: PWV during TT increased significantly compared to the basal and recovery phases (11.7 ± 2.5 m/s vs. 10.1 ± 2.3 m/s and 9.5 ± 2.0 m/s). Systolic BP (r = 0.55, r = 0.46 and r = 0.39) and age (r = 0.59, r = 0.63 and r = 0.39) correlated with PWV in all phases. The significance level for all tests was established as α = 0.05. Conclusion: We conclude that there is a permanent increase in PWV during orthostatic position that was returned to basal level at the recovery phase. This dynamic pattern of PWV response, during postural changes, can be explained by an increase in hydrostatic pressure at the level of abdominal aorta which with smaller radius and an increased elastic modulus, propagates the pulse in a faster way. Considering that it could increase central pulse reflection during the orthostatic position, we speculate that this mechanism may play a role in the overall adaptation of humans to gravitational stress.

Resumo Fundamento: A redução da complacência arterial tem sido associada ao envelhecimento e à hipertensão na postura supina. Entretanto, os efeitos dinâmicos do ortostatismo na distensibilidade aórtica não foram definidos. Objetivo: Determinar a influência ortostática e a interferência da idade, pressão arterial (PA) e frequência cardíaca (FC) sobre as grandes artérias durante o estresse gravitacional. Métodos: Noventa e três voluntários saudáveis (idade de 42 ± 16 anos). A velocidade da onda de pulso carotídeo-femoral (VOP), assumida como rigidez aórtica, foi avaliada na posição supina (fase basal) durante o teste de inclinação (TT) (fase ortostática) e após o retorno à posição supina (fase de recuperação). Simultaneamente à aquisição da PWV, registrou-se as medidas de PA e FC. Resultados: A VOP durante o TT aumentou significativamente em comparação com as fases basal e de recuperação (11,7 ± 2,5 m/s vs. 10,1 ± 2,3 m/se 9,5 ± 2,0 m/s). PA sistólica (r = 0,55, r = 0,46 e r = 0,39) e idade (r = 0,59, r = 0,63 e r = 0,39) correlacionaram-se com a VOP em todas as fases. O nível de significância para todos os testes foi estabelecido como = 0,05. Conclusão: Observou-se um aumento permanente da VOP durante a postura ortostática, que retornou ao nível basal na fase de recuperação. Esse padrão dinâmico de resposta da VOP, durante as alterações posturais, pode ser explicado pelo aumento da pressão hidrostática no nível da aorta abdominal que, com raio menor e aumento do módulo de elasticidade, propaga o pulso de maneira mais rápida. Considerando-se que poderia aumentar a reflexão do pulso central durante a posição ortostática, podemos especular que esse mecanismo pode desempenhar um papel na adaptação global do humano ao estresse gravitacional.

Women with Polycystic Ovarian Syndrome Exhibit Reduced Baroreflex Sensitivity That May Be Associated with Increased Body Fat / Mulheres com Síndrome do Ovário Policístico Apresentam menor Sensibilidade Barorreflexa, a Qual Pode Estar Associada ao Aumento da Gordura Corporal

Abstract Background: Polycystic ovarian syndrome (PCOS) women have a high prevalence of obesity and alterations in cardiovascular autonomic control, mainly modifications in heart rate variability (HRV) autonomic modulation. However, there are few studies about other autonomic control parameters, such as blood pressure variability (BPV) and baroreflex sensitivity (BRS). In addition, there are still doubts about the obesity real contribution in altering autonomic control in these women. Objective: To investigate BPV and BRS autonomic modulation alterations in PCOS women, as well as, to evaluate whether these alterations are due PCOS or increased body fat. Methods: We studied 30 eutrophic volunteers [body mass index (BMI) < 25 kg/m2] without PCOS (control group) and 60 volunteers with PCOS divided into: eutrophic (BMI < 25 kg/m2, N = 30) and obese women (BMI > 30 kg/m2, N = 30). All volunteers were submitted to anthropometric evaluation, hemodynamic and cardiorespiratory parameters record at rest and during physical exercise, analysis of HRV, BPV and spontaneous BRS. The differences in p less than 5% (p < 0.05) were considered statistically significant. Results: Related to eutrophics groups, there were no differences in autonomic parameters evaluated. The comparison between the PCOS groups showed that both PCOS groups did not differ in the BPV analysis. Although, the obese PCOS group presented lower values of spontaneous BRS and HRV, in low frequency and high frequency oscillations in absolute units. Conclusion: Our results suggest that obesity did little to alter HRV in women with PCOS, but it may influence the spontaneous BRS.

Resumo Fundamento: As mulheres com síndrome do ovário policístico (SOP) apresentam alta prevalência de obesidade e alterações no controle autonômico cardiovascular, principalmente modificações na modulação autonômica da variabilidade da frequência cardíaca (VFC). No entanto, existem poucos estudos sobre outros parâmetros de controle autonômico, como a variabilidade da pressão arterial (VPA) e a sensibilidade barorreflexa (SBR). Além disso, ainda há dúvidas sobre a real contribuição da obesidade na alteração do controle autonômico dessas mulheres. Objetivo: Investigar as alterações da modulação autonômica da VPA e SBR em mulheres com SOP, bem como avaliar se essas alterações se devem à SOP ou ao aumento da gordura corporal. Métodos: Foram estudadas 30 voluntárias com peso normal [índice de massa corporal (IMC) < 25 kg/m2] sem SOP (grupo controle) e 60 voluntárias com SOP, divididas em: mulheres com peso normal (IMC < 25 kg/m2, N = 30) e mulheres obesas (IMC > 30 kg/m2, N = 30). Todas as voluntárias foram submetidas à avaliação antropométrica, com registro de parâmetros hemodinâmicos e cardiorrespiratórios em repouso e durante exercício físico, e análise da VFC, VPA e SBR espontânea. As diferenças de p < 5% (p < 0,05) foram consideradas estatisticamente significantes. Resultados: Em relação aos grupos com peso normal, não houve diferenças nos parâmetros autonômicos avaliados. A comparação entre os grupos SOP mostrou que ambos os grupos não diferiram na análise da VPA. No entanto, o grupo SOP obeso apresentou menores valores de SBR espontânea e VFC nas oscilações de baixa e alta frequências, em unidades absolutas. Conclusão: Nossos resultados sugerem que a obesidade pouco influenciou a VFC em mulheres com SOP, mas pode afetar a SBR espontânea.

Baroreflex sensitivity in frailty syndrome

Frailty is related to a decrease in the physiological reserves, which causes difficulties in maintaining homeostasis. An example of physiological mechanisms for cardiovascular homeostasis is the baroreflex. The aim of this study was to compare baroreflex among frail, prefrail, and nonfrail individuals, in supine and orthostatic positions. Community-dwelling older adults were evaluated and categorized into frail, prefrail, or nonfrail groups, according to frailty phenotype. The RR interval (RRi) and systolic blood pressure (SBP) series were recorded for 15 min in the supine and 15 min in the orthostatic positions. Mean and variance of RRi and SBP, and baroreflex evaluated by phase, gain (α), and coherence (K2) were determined. A two-way repeated measures ANOVA, with Tukey's post hoc, was applied for group, position, and their interaction effects. The significance level established was 5%. Prefrail and frail participants did not present a significant decrease in mean values of RRi after postural challenge (893.43 to 834.20 ms and 925.99 to 857.98 ms, respectively). Frail participants showed a reduction in RRi variance in supine to orthostatic (852.04 to 232.37 ms2). Prefrail and frail participants showed a decrease in K2 after postural change (0.69 to 0.52 and 0.54 to 0.34, respectively). Frail participants exhibited lower values of K2 (0.34) compared to nonfrail and prefrail participants (0.61 and 0.52, respectively). Baroreflex indicated the presence of decoupling between heart period and SBP in frail and prefrail. Thus, reduced K2 might be a marker of the frailty process.

Impaired baroreflex sensitivity and increased systolic blood pressure variability in chronic post-ischemic stroke

OBJECTIVES: Acute post-stroke patients present cardiovascular autonomic dysfunction, which manifests as lower heart rate variability and impaired baroreflex sensitivity. However, few studies performed to date have evaluated cardiovascular autonomic function in chronic post-stroke patients. The aim of this study was to evaluate cardiovascular autonomic modulation in chronic post-ischemic stroke patients. METHODS: The seventeen enrolled subjects were divided into a stroke group (SG, n=10, 5±1 years after stroke) and a control group (CG, n=7). Non-invasive curves for blood pressure were continuously recorded (Finometer®) for 15 minutes while the subject was in a supine position. Heart rate variability and blood pressure variability were analyzed in the time and frequency domains. RESULTS: No differences were observed in systolic and diastolic pressure and heart rate between post-stroke patients and healthy individuals. The SG group had lower indexes for heart rate variability in the time domain (standard deviation of normal to normal R-R intervals, SDNN; variance of normal to normal R-R intervals, VarNN; and root mean square differences of successive R-R intervals, RMSSD) and a lower high-frequency band for heart rate variability than was observed in the CG. Systolic blood pressure variability and the low-frequency band for systolic pressure were higher in post-stroke patients, while the alpha index was lower in the SG than in the CG. CONCLUSION: After ischemic stroke, affected patients present chronically reduced heart rate variability, impaired cardiac vagal modulation, increased systolic blood pressure variability and higher sympathetic vascular modulation along with impaired baroreflex sensitivity, which can increase the risk of cardiovascular events, despite adequate blood pressure control.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

The Effect of Physical Resistance Training on Baroreflex Sensitivity of Hypertensive Rats / Efeito do Treinamento Físico Resistido na Sensibilidade Barorreflexa de Ratos Hipertensos

Abstract Background: Baroreceptors act as regulators of blood pressure (BP); however, its sensitivity is impaired in hypertensive patients. Among the recommendations for BP reduction, exercise training has become an important adjuvant therapy in this population. However, there are many doubts about the effects of resistance exercise training in this population. Objective: To evaluate the effect of resistance exercise training on BP and baroreceptor sensitivity in spontaneously hypertensive rats (SHR). Method: Rats SHR (n = 16) and Wistar (n = 16) at 8 weeks of age, at the beginning of the experiment, were randomly divided into 4 groups: sedentary control (CS, n = 8); trained control (CT, n = 8); sedentary SHR (HS, n = 8) and trained SHR (HT, n = 8). Resistance exercise training was performed in a stairmaster-type equipment (1.1 × 0.18 m, 2 cm between the steps, 80° incline) with weights attached to their tails, (5 days/week, 8 weeks). Baroreceptor reflex control of heart rate (HR) was tested by loading/unloading of baroreceptors with phenylephrine and sodium nitroprusside. Results: Resistance exercise training increased the soleus muscle mass in SHR when compared to HS (HS 0.027 ± 0.002 g/mm and HT 0.056 ± 0.003 g/mm). Resistance exercise training did not alter BP. On the other hand, in relation to baroreflex sensitivity, bradycardic response was improved in the TH group when compared to HS (HS -1.3 ± 0.1 bpm/mmHg and HT -2.6 ± 0.2 bpm/mmHg) although tachycardia response was not altered by resistance exercise (CS -3.3 ± 0.2 bpm/mmHg, CT -3.3 ± 0.1 bpm/mmHg, HS -1.47 ± 0.06 bpm/mmHg and HT -1.6 ± 0.1 bpm/mmHg). Conclusion: Resistance exercise training was able to promote improvements on baroreflex sensitivity of SHR rats, through the improvement of bradycardic response, despite not having reduced BP.

Resumo Fundamento: Os barorreceptores atuam como reguladores da pressão arterial (PA); no entanto, sua sensibilidade encontra-se prejudicada em pacientes hipertensos. Dentre as recomendações para a redução da PA, o treinamento físico tem se tornado um importante adjunto na terapia dessa população. Porém, ainda há diversos questionamentos sobre os efeitos de treinamento físico resistido nessa população. Objetivo: Avaliar o efeito do treinamento físico resistido na PA e na sensibilidade de barorreceptores em ratos espontaneamente hipertensos (SHR). Método: Ratos SHR (n = 16) e Wistar (n = 16) com 08 semanas de idade foram aleatoriamente divididos em 4 grupos: controle sedentário (CS, n = 8); controle treinado (CT, n = 8); SHR sedentário (HS, n = 8) e SHR treinado (HT, n = 8). O treinamento físico foi realizado em aparato com degraus (1,1 × 0,18 m, 2 cm entre os degraus, 80° inclinação) com peso fixado na cauda, (5 vezes por semana durante 8 semanas). O controle barorreflexo da frequência cardíaca (FC) foi testado com estímulos de fenilefrina e nitroprussiato de sódio. Resultados: O treinamento resistido foi capaz de aumentar a massa muscular do sóleo em ratos SHR (HS 0,027 ± 0,002 g/mm e HT 0,056 ± 0,003 g/mm). Não houve alteração da PA com o treinamento. Por outro lado, houve melhora na resposta bradicárdica da sensibilidade barorreflexa no grupo HT (HS -1,3 ± 0,1 bpm/mmHg e HT -2,6 ± 0,2 bpm/mmHg), no entanto, a resposta taquicárdica não foi alterada pelo exercício resistido (CS -3,3 ± 0,2 bpm/mmHg, CT -3,3 ± 0,1 bpm/mmHg, HS -1,47 ± 0,06 e HT -1,6 ± 0,1). Conclusão: O exercício físico resistido foi capaz de otimizar a sensibilidade barorreflexa dos ratos SHR por meio da melhora à resposta bradicárdica, apesar de não alterar a PA.

Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats / Modulação Serotoninérgica de Respostas Cardiovasculares Basais e Induzidas pela Expansão Isotônica do Volume Extracelular em Ratos

Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Baroreflex deficit are associated with target organ damage / Os déficits de barorreflexo estão associados ao dano do órgão alvo

As is well known, there are different pathophysiological conditions in which baroreflex deficit is enrolled in end-organ damage like hypertension, heart failure and myocardial infarction. The purpose of this study was to investigate the mechanisms enrolled in those relationships using a baroreflex deficit­induced model. Sinoaortic-denervated (SAD) rats were used as a model of arterial baroreflex impairment. Male Wistar rats were divided into: control (n = 9), and SAD (n = 8, 30 days) groups. SAD was performed using the method previously described by Krieger (1964). Cardiac morphology was assessed by echocardiography BP, HR and BP, and pulse interval (PI) variabilities were analyzed using a data acquisition system (Codas, 2kHz). Stroke volume and peripheral and regional resistance were evaluated using colored microspheres. SAD induced LV hypertrophy estimated by LV/BW mass using echocardiography. BP (C: 106±0.6 vs. SAD: 108±2 mmHg) and HR (C: 355±7 vs. SAD: 357±15 bpm) were not modified by SAD, while BP variability (C: 6.2±0.84 vs SAD: 14±0.9 mmHg) and PI variability (C: 24±0.7 vs SAD:17±0.8 ms) were increased and decreased, respectively. Moreover, a reduction was observed in stroke volume (C: 0.31±0.02 vs SAD: 0.25±0.01 mL/ min) and an increase in total peripheral resistance (C: 0.97±0.07 vs. SAD: 1.23±0.07 mL/min/mmHg) in SAD animals. Those alterations resulted in increased cardiac vascular resistance (C: 35±1.6 vs. SAD:66±2.3 mmHg/mL/min/g) and renal vascular resistance (C: 31±1.2 vs. SAD: 75±2.2 mmHg/mL/min/g) in the SAD group. SAD induced an augment in cardiac and renal damage as cardiac morphology by histological techniques showed increased arterial wall and interstitial fibroses, and renal morphology showed interstitial fibroses and a decreased Bowmann space. Conclusion: Total baroreflex dysfunction impaired BP and HR variabilities associated with decreased stroke volume and increased peripheral and regional resistance. These adjustments may play an important role in target organ damage in different pathological conditions; even BP values were maintained at the control levels

Existem diferentes condições fisiopatológicas em que o déficit de barorreflexo está associado ao dano do órgão final, como hipertensão, insuficiência cardíaca e infarto do miocárdio. O objetivo deste estudo foi investigar os mecanismos inscritos nestes relacionamentos usando um modelo induzido por déficit de barorreflexo. Foram utilizados ratos com desnervação sino-aórtica (SAD) como modelo de comprometimento barorreflexo arterial. Os ratos Wistar machos foram divididos em grupos controle (n = 9) e SAD (n = 8, 30 dias). O SAD foi realizado utilizando o método anteriormente descrito por Krieger (1964). A morfologia cardíaca foi avaliada pela ecocardiografia PA, e as variabilidades de FC e PA, e do intervalo de pulso (IP) foram analisadas usando um sistema de aquisição de dados (Codas, 2kHz). O volume sistólico e a resistência periférica e regional foram avaliados utilizando microesferas coloridas. SAD induziu hipertrofia do VE estimada pela massa de VE/PC usando ecocardiografia. PA (C: 106±0,6 vs. SAD: 108±2 mmHg) e FC (C: 355±7 vs. SAD: 357±15 bpm) não foram modificados pelo SAD, enquanto a variabilidade da PA (C: 6,2±0,84 vs. SAD: 14±0,9 mmHg) e a variabilidade de PI (C: 24±0,7 vs. SAD: 17±0,8 ms) aumentaram e diminuíram, respectivamente. Além disso, observou-se uma redução no volume sistólico (C: 0,31± 0,02 vs SAD: 0,25 ± 0,01 mL/min) e um aumento na resistência periférica total (C: 0,97±0,07 vs. SAD: 1,23±0,07 mL/min/mmHg) em animais SAD. Essas alterações resultaram em aumento da resistência vascular cardíaca (C: 35±1,6 vs. SAD: 66 ± 2,3 mmHg/mL/min/g) e resistência vascular renal (C: 31±1,2 vs. SAD: 75±2,2 mmHg/mL/min/g) no grupo SAD. SAD induziu um aumento no dano cardíaco e renal como a morfologia cardíaca por técnicas histológicas mostrou aumento da parede arterial e fibrose intersticial, e a morfologia renal mostrou fibrose intersticial e uma diminuição do espaço de Bowmann. A disfunção barorreflexa total prejudicou as variabilidades de PA e FC associadas à diminuição do volume sistólico e ao aumento da resistência periférica e regional. Esses ajustes podem desempenhar um papel importante no dano de órgãos alvo em diferentes condições patológicas; até mesmo os valores da PA foram mantidos nos níveis de controle

Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.

Cardiovascular coupling during graded postural challenge: comparison between linear tools and joint symbolic analysis

ABSTRACT Background A joint symbolic analysis (JSA) is applied to assess the strength of the cardiovascular coupling from spontaneous beat-to-beat variability of the heart period (HP) and the systolic arterial pressure (SAP) during an experimental protocol inducing a gradual baroreflex unloading evoked by postural change (i.e. graded head-up tilt). Method: The adopted JSA can quantify the degree of association between the HP and SAP variabilities as a function of the time scale of the HP and SAP patterns. Traditional linear tools assessing the HP-SAP coupling strength, such as squared correlation coefficient, squared coherence function, and percentage of baroreflex sequences, were computed as well for comparison. Results: We found that: i) JSA indicated that the strength of the cardiovascular coupling at slow temporal scales gradually increased with the magnitude of the orthostatic challenge, while that at fast temporal scales gradually decreased; ii) the squared correlation coefficient and percentage of baroreflex sequences did not detect this behavior; iii) even though squared coherence function could measure the magnitude of the HP-SAP coupling as a function of the time scale, it was less powerful than JSA owing to the larger dispersion of the frequency domain indexes. Conclusion: Due to its peculiar features and high statistical power, JSA deserves applications to pathological groups in which the link between HP and SAP variabilities is lost or decreased due to the overall depression or impairment of the cardiovascular control.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Cardiac Autonomic Adjustments During Baroreflex Test in Obese and Non-Obese Preadolescents / Ajustes Autonômicos Cardíacos Durante Teste Barorreflexo em Pré-Adolescentes Obesos e Não Obesos

Abstract Background: Recent studies have shown changes in cardiac autonomic control of obese preadolescents. Objective: To assess the heart rate responses and cardiac autonomic modulation of obese preadolescents during constant expiratory effort. Methods: This study assessed 10 obese and 10 non-obese preadolescents aged 9 to 12 years. The body mass index of the obese group was between the 95th and 97th percentiles of the CDC National Center for Health Statistics growth charts, while that of the non-obese group, between the 5th and 85th percentiles. Initially, they underwent anthropometric and clinical assessment, and their maximum expiratory pressures were obtained. Then, the preadolescents underwent a constant expiratory effort of 70% of their maximum expiratory pressure for 20 seconds, with heart rate measurement 5 minutes before, during and 5 minutes after it. Heart rate variability (HRV) and heart rate values were analyzed by use of a software. Results: The HRV did not differ when compared before and after the constant expiratory effort intra- and intergroup. The heart rate values differed (p < 0.05) during the effort, being the total variation in non-obese preadolescents of 18.5 ± 1.5 bpm, and in obese, of 12.2 ± 1.3 bpm. Conclusion: The cardiac autonomic modulation did not differ between the groups when comparing before and after the constant expiratory effort. However, the obese group showed lower cardiovascular response to baroreceptor stimuli during the effort, suggesting lower autonomic baroreflex sensitivity.

Resumo Fundamento: Estudos recentes revelaram alterações no controle autonômico cardíaco de pré-adolescentes obesos. Objetivo: Avaliar as respostas de frequência cardíaca e modulação autonômica cardíaca de pré-adolescentes obesos durante esforço expiratório constante. Métodos: Estudaram-se 10 pré-adolescentes obesos e 10 não obesos com idades entre 9 e 12 anos. O índice de massa corporal dos obesos esteve entre os percentis 95 e 97 das curvas do gráfico do National Center for Health Statistics, enquanto o de não obesos, entre os percentis 5 e 85. Inicialmente, realizaram-se avaliações antropométrica e clínica, e as pressões expiratórias máximas foram obtidas. A seguir, os pré-adolescentes foram submetidos a um esforço expiratório constante correspondendo a 70% das pressões expiratórias máximas por 20 segundos, com registro da frequência cardíaca 5 minutos antes e depois do esforço, e durante o mesmo. A variabilidade e os valores de frequência cardíaca foram analisados em um software. Resultados: Os índices da variabilidade da frequência cardíaca não diferiram ao serem comparados antes e depois do esforço expiratório constante intra- e intergrupos. Os valores da frequência cardíaca diferiram (p < 0,05) durante o esforço, sendo a variação total nos não obesos de 18,5 ± 1,5 bpm e nos obesos, 12,2 ± 1,3 bpm. Conclusão: A modulação autonômica cardíaca não diferiu entre os grupos antes e depois do esforço expiratório constante. No entanto, o grupo de obesos mostrou menor resposta cardiovascular ao estímulo barorreceptor durante o esforço, o que sugere menor sensibilidade autonômica barorreflexa.

Mecanismos associados ao desenvolvimento das complicações cardiometabólicas em SHR submetidos à sobrecarga de frutose: papel do treinamento físico aeróbio / Mechanisms associated with cardiometabolic dysfunctions development in SHR submitted to fructose overload: role of aerobic exercise training

Neste estudo testamos a hipótese que alterações no controle autonômico precedem alterações cardiometabólicas em animais espontaneamente hipertensos tratados com frutose (SHR). Adicionalmente avaliamos os efeitos do treinamento físico aeróbio (TFA) no curso temporal das disfunções observadas neste modelo de síndrome metabólica. Para isso, foram utilizados ratos machos Wistar e SHR divididos em grupos (n=8): Controle (C), Hipertenso (H), Hipertenso+Frutose (HF) e Hipertenso+Frutose+Treinamento Físico (HFT). A sobrecarga de frutose (100g/L) e o TFA (esteira: 1h/d., 5d/sem.) foram iniciados 30 dias após o nascimento dos animais. Os grupos experimentais foram divididos em subgrupos que foram avaliados após 7, 15, 30 e 60 dias de protocolo. A partir dos 7 dias de protocolo a associação da hipertensão ao consumo de frutose (grupo HF) induziu redução da sensibilidade barorreflexa para respostas bradicárdicas (RB) e taquicárdicas (RT) em comparação ao grupo C; observando-se redução adicional da RB no grupo HF em relação ao grupo H (7 dias: -40% e 15 dias: -36%). A reatividade vascular à fenilefrina (8ug/ml: 7 aos 60 dias) estava prejudicada nos grupos H e HF em relação ao C; com prejuízo adicional do grupo HF ao nitroprussiato de sódio na dose de 20ug/ml (15 aos 60 dias de protocolo vs. C). Além disso, aos 15 e 30 dias de protocolo, o grupo HF apresentou um aumento marcante do TNFalfa e IL-6 no tecido adiposo e de IL-1beta no baço em relação aos grupos C e H. Houve redução de nitritos plasmáticos no grupo HF em 15 (55%) e 30 dias (58%) vs. o grupo C, acompanhado de aumento do peróxido de hidrogênio em 30 dias vs. o grupo H (98%). Em relação as defesas antioxidantes, o grupo HF apresentou menor atividade da superóxido dismutase (SOD) vs. os grupos C (15 dias: 36%, 30 dias: 31% e 60 dias: 47%) e H (15 dias: 25%, 30 dias: 21% e 60 dias: 43%), sem alterações significantes na catalase e no potencial antioxidante total. O grupo HF teve maior lipoperoxidação e oxidação de...

This study tested the hypothesis that changes in autonomic control precede cardiometabolic changes in spontaneously hypertensive rats (SHR) treated with fructose. Additionally, the effects of aerobic exercise training (AET) were evaluated in the time course of the dysfunctions observed in this metabolic syndrome model. Wistar and SHR rats were divided into groups (n=8/group): control (C), hypertensive (H), hypertensive + fructose (HF) and hypertensive + fructose + AET (HFT). The fructose overload (100g/l) and the AET (treadmill 1h/d, 5d/wk) was initiated at 30 days of life. The experimental groups were divided into subgroups, which were evaluated after 7, 15, 30 and 60 days of protocol. Since 7 day of protocol the association of hypertension and fructose consumption (HF group) induced a reduction in baroreflex sensitivity for bradycardic (BR) and tachycardia responses (TR) when compared to the C group; there was an additional reduction of BR in the HF group when compared to the H group (7 days: 40% and 15 days: 36%). The vascular reactivity to phenylephrine (8ug/ml: 7 to 60 days) was impaired in H and HF groups when compared to the C group; it was observed an additional impairment in the HF group to sodium nitroprusside at the dose of 20?g/ml (15 to 60 days of protocol vs. C). Additionally, at 15 and 30 day of protocol, the HF group showed an increase in TNFalfa and IL-6 in adipose tissue and in IL-1beta in the spleen when compared to C and H groups. There was a reduction in plasma nitrites in the HF group in 15 (55%) and 30 days of protocol (58%) vs. the C group, accompanied by an increase of the hydrogen peroxide in 30 days vs. H group (98%). Regarding the antioxidant defenses, the HF group showed reduced superoxide dismutase (SOD) activity as compared to C (15 days: 36%, 30 days: 31% and 60 days: 47%) and H groups (15 days: 25% 30 days: 21% and 60 days: 43%), without significant changes in catalase and in total antioxidant potential. The HF group had...

Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.