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.

Cellular and Molecular Mechanisms Underlying Arterial Baroreceptor Remodeling in Cardiovascular Diseases and Diabetes / 神经科学通报·英文版

Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.

Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway / 神经科学通报·英文版

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.

Baroreflex Control of Heart Rate in Mice Overexpressing Human SOD1: Functional Changes in Central and Vagal Efferent Components / 神经科学通报·英文版

Excessive reactive oxygen species (ROS) (such as the superoxide radical) are commonly associated with cardiac autonomic dysfunctions. Though superoxide dismutase 1 (SOD1) overexpression may protect against ROS damage to the autonomic nervous system, superoxide radical reduction may change normal physiological functions. Previously, we demonstrated that human SOD1 (hSOD1) overexpression does not change baroreflex bradycardia and tachycardia but rather increases aortic depressor nerve activity in response to arterial pressure changes in C57B6SJL-Tg (SOD1)2 Gur/J mice. Since the baroreflex arc includes afferent, central, and efferent components, the objective of this study was to determine whether hSOD1 overexpression alters the central and vagal efferent mediation of heart rate (HR) responses. Our data indicate that SOD1 overexpression decreased the HR responses to vagal efferent nerve stimulation but did not change the HR responses to aortic depressor nerve (ADN) stimulation. Along with the previous study, we suggest that SOD1 overexpression preserves normal baroreflex function but may differentially alter the functions of the ADN, vagal efferents, and central components. While SOD1 overexpression likely enhanced ADN function and the central mediation of bradycardia, it decreased vagal efferent control of HR.

Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii / 神经科学通报·英文版

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.

Heart Rate Variability Biofeedback Increased Autonomic Activation and Improved Symptoms of Depression and Insomnia among Patients with Major Depression Disorder

OBJECTIVE: Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia. METHODS: In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up. RESULTS: In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values. CONCLUSION: This study confirmed that HRV-BF is a useful psychosocial intervention for improving autonomic balance, baroreflex, and symptoms of depression and insomnia in MDD patients.

Evaluation of efficacy of Valsalva maneuver for attenuating propofol injection pain: a prospective, randomized, single blind, placebo controlled study / 대한마취과학회지

BACKGROUND: Pain on injection is a limitation with propofol use. The effect of the Valsalva maneuver on pain during propofol injection has not been studied. This maneuver reduces pain through the sinoaortic baroreceptor reflex arc and by distraction. We aimed to assess the efficacy of the Valsalva maneuver in reducing pain during propofol injection. METHODS: Eighty American Society of Anesthesiologists class I adult patients undergoing general anesthesia were enrolled and divided into two groups of 40 each. Group I (Valsalva) patients blew into a sphygmomanometer tube raising the mercury column up to 30 mmHg for 20 seconds, while Group II (Control) patients did not. Anesthesia was induced with 1% propofol immediately afterwards. Pain was assessed on a 10-point visual analog scale (VAS), where 0 represented no pain, and 10, the worst imaginable pain, and a 4-point withdrawal response score, where 0 represented no pain, and 3, the worst imaginable pain. Scores were presented as median (interquartile range). RESULTS: We analyzed the data of 70 patients. The incidence of pain was significantly lower in the Valsalva than in the control group (53% vs 78%, P = 0.029). The withdrawal response score was significantly lower in the Valsalva group (1.00 [0.00-1.00] vs 2.00 [2.00-3.00], P < 0.001). The VAS score was significantly lower in the Valsalva group (1.00 [0.00-4.00] vs 7.00 [6.25-8.00], P < 0.001). CONCLUSIONS: A prior Valsalva maneuver is effective in attenuating injection pain due to propofol; it is advantageous in being a non-pharmacological, safe, easy, and time-effective technique.

Hemodynamic, Autonomic, and Vascular Function Changes after Sleep Deprivation for 24, 28, and 32 Hours in Healthy Men

This study aimed to analyze the impact of sleep deprivation (SD) on cardiac, hemodynamic, and endothelial parameters and to determine whether these are sustained with increased periods of SD. The study included 60 healthy men (mean: age 31.2±6.3 years; body mass index 24.6±2.6 kg/m2). Hemodynamic parameters, parameters of myocardial contractility, spectral analysis of heart rate (HR) and blood pressure (BP) variability, and the sensitivity of arterial baroreflex function were evaluated. Biochemical tests were performed to assess L-arginine (L-Arg) and asymmetric dimethylarginine (ADMA) levels in reflection of endothelial nitric oxide synthase ability. Measurements of cardiovascular system parameters were obtained at 9 a.m. (baseline) on the first day of the study and 9 a.m. (24-h SD), 1 p.m. (28-h SD), and 5 p.m. (32-h SD) on the second day. Blood samples for evaluating biochemical parameters were obtained at baseline and after 24-h SD. ANOVA Friedman's test revealed a significant effect for time in relation to HR (χ²=26.04, df=5, p=0.000), systolic BP (χ²=35.98, df=5, p=0.000), diastolic BP (χ²=18.01, df=5, p=0.003), and mean BP (χ²=28.32, df=5, p=0.000). L-Arg and ADMA levels changed from 78.2±12.9 and 0.3±0.1 at baseline to 68.8±10.2 and 0.4±0.1 after 24-hr SD, respectively (p=0.001, p=0.004). SD in healthy men is associated with increases in BP, which appear to occur after 24 hours of SD and are maintained over increasing periods of SD. The observed hemodynamic changes may have resulted due to disordered vascular endothelial function, as reflected in alterations in L-Arg and ADMA levels.

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.