Role of corticotropin-releasing factor neurotransmission in the lateral hypothalamus on baroreflex impairment evoked by chronic variable stress in rats.

Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF2, but not CRF1, receptor expression within the LH. Local microinjection of either CRF1 or CRF2 receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.

Effect of walk training combined with blood flow restriction on resting heart rate variability and resting blood pressure in middle-aged men

Aim: To investigate the effects of low-intensity walk training with and without blood flow restriction (BRF) on resting heart rate variability (HRV) and blood pressure (BP) in middle-aged men. Methods: Twenty-one men were randomly assigned into the walk training group with (BRF-W; n = 11) and without (NOR-W; n = 10) BFR. The resting HRV and blood pressure were assessed pre- and post-6 weeks of the intervention [3 times/week, 5 sets of 3-min walking (6 km.h-1) with 1-min of rest, totalizing 18 sessions of training]. The BFR-W group received the occlusive stimulus before of training sessions though of a standard sphygmomanometer and performed the training sessions with the vascular occlusion (80-100 mmHg) in both the legs. Results: Only BRF-W group improved HRV on time domain indices (SDNN and RMSSD; p < 0.05) after training but it was not found differences on frequency domain indices. In addition, systolic blood pressure (SBP) improved after training (PRE: 128.5 ± 5.9 vs POST: 119.1 ± 8.6 mmHg; Cohen's d = -1.30; p < 0.01) only in BFR-W group. There was not a significant difference on diastolic blood pressure (DBP) after training, however, effect size was moderate for BFR-W (Cohen's d = -0.56; p > 0.05). Conclusion: Our results showed that walking training with blood flow restriction can improve health cardiovascular parameters in middle-aged men.(AU)

Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats.

This study investigated neuroendocrine, autonomic, and cardiovascular changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in 60-days-old female normotensive Wistar rats and female spontaneously hypertensive rats (SHR). Both strains of rats were exposed for 10 consecutive days to either the homotypic stressor repeated restraint stress (RRS) or the heterotypic stressor chronic unpredictable stress (CUS). As expected, SHR had higher baseline blood pressure values and impaired baroreflex activity in relation to normotensive animals. Besides, SHR presented higher plasma corticosterone levels and decreased thymus weight. Both RRS and CUS increased baseline plasma corticosterone concentration and decreased body weight gain in both normotensive and SHR rats. In addition, both stress protocols caused hypertrophy of adrenal glands in normotensive rats. Regarding the cardiovascular effects, RRS increased basal heart rate in both rat strains, which was mediated by an increase in sympathetic tone to the heart. Besides, RRS increased baroreflex-mediated tachycardia in SHR animals, while CUS increased cardiac parasympathetic activity and pacemaker activity in normotensive rats. Taken together, these results indicate a stress type-specific effect, as identified by a vulnerability of both strains to the deleterious cardiovascular effects evoked by the homotypic stressor and a resilience to the impact of the heterotypic stressor. Vulnerability of hypertensive rats was evidenced by the absence of CUS-evoked adaptive cardiovascular responses and an increase of baroreflex tachycardia in SHR animals subjected to RRS. The somatic and HPA axis changes were overall independent of the chronic stress regimen and pre-existing hypertension.

Cardiovascular and metabolic consequences of the association between chronic stress and high-fat diet in rats.

Obesity and chronic stress are considered independent risk factors for the development of cardiovascular diseases and changes in autonomic system activity. However, the cardiovascular consequences induced by the association between high-fat diet (HFD) and chronic stress are not fully understood. We hypothesized that the association between HFD and exposure to a chronic variable stress (CVS) protocol for four weeks might exacerbate the cardiovascular and metabolic disturbances in rats when compared to these factors singly. To test this hypothesis, male Wistar rats were divided into four groups: control-standard chow diet (SD; n = 8); control-HFD (n = 8); CVS-SD (n = 8); and CVS-HFD (n = 8). The CVS consisted of repeated exposure of the rats to different inescapable and unpredictable stressors (restraint tress; damp sawdust, cold, swim stress and light cycle inversion). We evaluated cardiovascular function, autonomic activity, dietary intake, adiposity and metabolism. The HFD increased body weight, adiposity and blood glucose concentration (∼15%) in both control and CVS rats. The CVS-HFD rats showed decreased insulin sensitivity (25%) compared to CVS-SD rats. The control-HFD and CVS-HFD rats presented increased intrinsic heart rate (HR) values (∼8%). CVS increased cardiac sympathetic activity (∼65%) in both SD- and HFD-fed rats. The HFD increased basal HR (∼10%). Blood pressure and baroreflex analyzes showed no differences among the experimental groups. In conclusion, the present data indicate absence of interaction on autonomic imbalance evoked by either CVS or HFD. Additionally, HFD increased HR and evoked metabolic disruptions which are independent of stress exposure.

Sex differences in cardiovascular, neuroendocrine and behavioral changes evoked by chronic stressors in rats.

This study investigated the physiological, somatic and behavioral changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in male and female rats. For this, adult Wistar rats were subjected to a 10days regimen of repeated restraint stress (RRS, homotypic stressor) or chronic variable stress (CVS, heterotypic stressor). Effects evoked by CVS included: (i) adrenal hypertrophy and decreased body weight gain in male animals, (ii) a sympathetically-mediated increase in basal heart rate in males, and (iii) a rise in plasma corticosterone concentration and anxiogenic effects in female animals. The homotypic stressor RRS also induced an increase in plasma corticosterone and anxiogenic effects in females, decreased body weight gain in males and evoked a sympathetically-mediated increase in heart rate in both sexes. Changes in cardiovascular function and autonomic activity evoked by both stressors were followed by impairment of baroreflex activity in males, but not female animals. Both chronic stressors evoked changes in blood pressure responsiveness to vasoconstrictor and vasodilator agents in both sexes. Taken together, these results indicate that regardless of chronic stress regimen males are more vulnerable to somatic effects of chronic stressors, while females appear to be more susceptible to neuroendocrine and behavioral changes. Present findings also indicate that females are selectively vulnerable to cardiovascular and autonomic changes evoked by homotypic stressors. Nevertheless, homotypic and heterotypic stressors similarly affect cardiovascular function and autonomic activity in males.

Both N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors in the bed nucleus of the stria terminalis modulate the cardiovascular responses to acute restraint stress in rats.

The bed nucleus of the stria terminalis (BNST) is a forebrain structure that has been implicated on cardiovascular responses evoked by emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully described. In our study we investigated the involvement of glutamatergic neurotransmission within the BNST in cardiovascular changes evoked by acute restraint stress in rats. For this study, we investigated the effects of bilateral microinjections of selective antagonists of either N-methyl-D-aspartate (NMDA) or non-NMDA glutamate receptors into the BNST on the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by acute restraint stress. Microinjection of the selective NMDA glutamate receptor antagonist LY235959 (1 nmol/100 nL) into the BNST decreased the tachycardiac response to restraint stress, without affecting the arterial pressure increase and the drop in skin temperature. Bilateral BNST treatment with the selective non-NMDA glutamate receptor NBQX (1 nmol/100 nL) decreased the heart rate increase and the fall in tail skin temperature, without affecting the blood pressure increase. These findings indicate a facilitatory influence of BNST glutamatergic neurotransmission via coactivation of local NMDA and non-NMDA receptors on the tachycardiac response to stress, whereas control of sympathetic-mediated cutaneous vasoconstriction is selectively mediated by local non-NMDA glutamate receptors.

Exogenous oxytocin reduces signs of sickness behavior and modifies heart rate fluctuations of endotoxemic rats.

Besides the well-known roles of oxytocin on birth, maternal bonding, and lactation, recent evidence shows that this hypothalamic hormone possesses cardioprotective, anti-inflammatory and parasympathetic neuromodulation properties. In this study, we explore the heart rate fluctuations (HRF) in an endotoxemic rodent model that was accompanied by the administration of exogenous oxytocin. The assessment of HRF has been widely used as an indirect measure of the cardiac autonomic function. In this context, adult male Dark Agouti rats were equipped with a telemetric transmitter to continuously and remotely measure the electrocardiogram, temperature, and locomotion. In a between-subjects experimental design, rats received the following peripheral treatment: saline solution as a vehicle (V); lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide + oxytocin (LPS+Ox). Linear and non-linear parameters of HRF were estimated starting 3h before to 24h after treatments. Our results showed that exogenous oxytocin does not modify by itself the HRF of oxytocin-treated rats in comparison to vehicle-treated rats. However, in animals undergoing endotoxemia it: a) provokes a less anticorrelated pattern in HRF, b) decreased mean heart rate, c) moderated the magnitude and duration of the LPS-induced hyperthermia, and d) increased locomotion, up to 6h after the LPS injection. The less anticorrelated pattern in the HRF and decreased mean heart rate may reflect a cardiac pacemaker coupling with cholinergic influences mediated by oxytocin during LPS-induced endotoxemia. Finally, the anti-lethargic and long-term temperature moderating effects of the administration of oxytocin during endotoxemia could be a consequence of the systemic anti-inflammatory properties of oxytocin.

Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type.

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress.

Monitoring weekly heart rate variability in futsal players during the preseason: the importance of maintaining high vagal activity.

This study aimed to compare the weekly natural log of the root-mean-square difference of successive normal inter-beat (RR) intervals (ln RMSSDWeekly) and its coefficient of variation (ln RMSSDCV) in response to 5 weeks of preseason training in professional male futsal players. A secondary aim was to assess the relationship between ln RMSSDWeekly and ln RMSSDCV. The ln RMSSD is a measure of cardiac-vagal activity, and ln RMSSDCV represents the perturbations of cardiac autonomic homeostasis, which may be useful for assessing how athletes are coping with training. Ten futsal players had their resting ln RMSSD recorded prior to the first daily training session on four out of approximately five regular training days · week-1. Session rating of perceived exertion (sRPE) was quantified for all training sessions. Despite weekly sRPE varying between 3455 ± 300 and 5243 ± 463 arbitrary units (a.u.), the group changes in ln RMSSDWeekly were rated as unclear (using magnitude-based inference), although large inter-individual variability in ln RMSSD responses was observed. The ln RMSSDCV in weeks 4 and 5 were likely lower than the previous weeks. A large and significant negative correlation (r = -0.53; CI 90%: -0.36; -0.67) was found between ln RMSSD and ln RMSSDCV. Therefore, monitoring individual ln RMSSD responses is suggested since large inter-individual variations may exist in response to futsal training. In addition, higher values of ln RMSSD are associated with lower oscillations of cardiac autonomic activity.

A comparison of heart rate variability in women at the third trimester of pregnancy and during low-risk labour.

Heart rate variability (HRV) has been recognised as a non-invasive method for assessing cardiac autonomic regulation. Aiming to characterize HRV changes at labour in women, we studied 10 minute ECG recordings from young mothers (n=30) at the third trimester of pregnancy (P) or during augmentation of labour (L) (n=30). Data of the L group were collected when no-contractions (L-NC) or the contractile activity (L-C) was manifested. Accordingly, the inter-beat interval (IBI) time series were processed to estimate relevant parameters of HRV such as the mean IBI (IBI¯), the mean heart rate HR¯, the root mean square of successive differences (RMSSD) in IBIs, the natural logarithm of high-frequency component (LnHF), the short-term scaling parameters from detrended fluctuation and magnitude and sign analyses such as (α1, α1(MAG), α1(SIGN)), and the sample entropy (SampEn). We found statistical differences (p<0.05) for RMSSD among P and L-NC/L-C groups (25 ± 13 vs. 36 ± 14/34 ± 16 ms) and for LnHF between P and L-NC (5.37 ± 1.15 vs. 6.05 ± 0.86 ms(2)). Likewise, we identified statistical differences (p<0.05) for α1(SIGN) among P and L-NC/L-C groups (0.19 ± 0.20 vs. 0.32 ± 0.17/0.39 ± 0.13). By contrast, L-NC and L-C groups showed statistical differences (p<0.05) in α1(MAG) (0.67 ± 0.12 vs. 0.79 ± 0.12), and SampEn (1.62 ± 0.26 vs. 1.20 ± 0.44). These results suggest that during labour, despite preserving a concomitant non-linear influence, the maternal short-term cardiac autonomic regulation becomes weakly anticorrelated (as indicated by α1(SIGN)); furthermore, an increased vagally mediated activity is observed (as indicated by RMSSD and LnHF), which may reflect a cholinergic pathway activation owing to the use of oxytocin or the anti-inflammatory cholinergic response triggered during labour.

CRF1 and CRF2 receptors in the bed nucleus of the stria terminalis modulate the cardiovascular responses to acute restraint stress in rats.

The corticotropin-releasing factor (CRF) is involved in behavioral and physiological responses to emotional stress through its action in several limbic structures, including the bed nucleus of the stria terminalis (BNST). Nevertheless, the role of CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during aversive threat is unknown. Therefore, in the present study we investigated the involvement of CRF receptors within the BNST in cardiovascular responses evoked by acute restraint stress in rats. For this, we evaluated the effects of bilateral treatment of the BNST with selective agonists and antagonists of either CRF1 or CRF2 receptors in the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by restraint stress. Microinjection of the selective CRF1 receptor antagonist CP376395 into the BNST reduced the pressor and tachycardiac responses caused by restraint. Conversely, BNST treatment with the selective CRF1 receptor agonist CRF increased restraint-evoked arterial pressure and HR responses and reduced the fall in tail skin temperature response. All effects of CRF were inhibited by local BNST pretreatment with CP376395. The selective CRF2 receptor antagonist antisalvagine-30 reduced the arterial pressure increase and the fall in tail skin temperature. The selective CRF2 receptor agonist urocortin-3 increased restraint-evoked pressor and tachycardiac responses and reduced the drop in cutaneous temperature. All effects of urocortin-3 were abolished by local BNST pretreatment with antisalvagine-30. These findings indicate an involvement of both CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during emotional stress.

NMDA receptors in the lateral hypothalamus have an inhibitory influence on the tachycardiac response to acute restraint stress in rats.

The aim of the present study was to investigate the role of the lateral hypothalamus (LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor CoCl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate (HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl-d-aspartate (NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of CoCl2 . No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non-NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress.

Respostas cardiovasculares a mudança postural e capacidade aeróbia em homens e mulheres de meia-idade antes e após treinamento físico aeróbio / Cardiovascular responses to postural change and aerobic capacity among middle-aged men and women before and after aerobic physical training

OBJETIVO: Comparar respostas cardiovasculares a Manobra Postural Passiva (Tilt Test) e capacidade cardiorrespiratória em homens e mulheres de meia-idade antes e após treinamento físico aeróbio. MATERIAIS E MÉTODOS: Sete homens - GH (44,6±2,1 anos) e sete mulheres - GM (51,7±4,8 anos), participaram de treinamento físico aeróbio por 12 semanas. Foi realizado protocolo de Tilt Test (cinco minutos supino, dez minutos inclinado 70º, cinco minutos supino), com monitoração da pressão arterial e freqüência cardíaca. Para mensuração da capacidade cardiorrespiratória foi realizado protocolo em cicloergômetro. RESULTADOS: Na condição sedentária, GH mostrou maior influência parassimpática no controle da freqüência cardíaca evidenciada por maior intervalo RR (iRR) durante Tilt Test. Na condição treinada, os valores de iRR de ambos os grupos se assemelham, tendo as mulheres iRR maior em supino, mas na inclinação os homens mantêm iRR mais elevado. Para pressão arterial, as mulheres permanecem com valores superiores após treino, mas a freqüência cardíaca tende a se assemelhar em ambos. Já na capacidade cardiorrespiratória, homens e mulheres têm um padrão de comportamento semelhante após treino. Com exceção dos valores absolutos da freqüência cardíaca, sem diferenças entre os grupos, para todas as outras variáveis os homens obtiveram valores superiores aos das mulheres. Observa-se ainda que, após o treinamento, houve redução significativa dos valores de pressão arterial no GM, mesmo continuando superiores aos dos homens. CONCLUSÃO: O treinamento parece ter reduzido os níveis pressóricos nas mulheres, além de serem observadas melhorias na capacidade cardiorrespiratória de ambos os grupos, permanecendo os homens com melhor desempenho do que as mulheres.

OBJECTIVE: To compare the cardiovascular responses to passive postural maneuvers (tilt test) and the cardiorespiratory capacity in middle-aged men and women, before and after aerobic physical training. METHODS: Seven men (44.6±2.1 years old) and seven women (51.7±4.8 years old) participated in aerobic physical training for 12 weeks. The tilt test protocol (five minutes supine, ten minutes tilted at 70º and five minutes supine) was followed, with arterial blood pressure and heart rate monitoring. A cycle ergometer protocol was used to measure cardiorespiratory capacity. RESULTS: In the sedentary condition, men showed greater parasympathetic influence in heart rate control, as demonstrated by their higher RR interval (iRR) during the tilt test. After training, the iRR values became more similar in the two groups, although the women had higher iRR in the supine position and the men continued to present higher iRR under tilted conditions. The women's blood pressures continued to be higher after training, but heart rate tended to become similar in the two groups. The cardiorespiratory capacity patterns in the two groups were similar after training. Except for absolute heart rate values, for which there were no differences between the groups, the men's values were higher than those of the women for all other variables. It was also observed that, after the training, the women's blood pressures were significantly lower, even though their pressures remained higher than the men's. CONCLUSIONS: The training seemed to reduce the women's arterial blood pressure levels and improve both groups' cardiorespiratory capacity, but the men continued to present better performance than the women.