Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function: a population based study

Oxytocin (OT) is a nonapeptide neurohormone that is involved in a broad array of physiological and behavioral processes related to health including hypothalamic-pituitary-adrenal (HPA) axis functioning, autonomic nervous system (ANS) activity and social behaviors. The present study sought to explore the influence of genetic variation in the oxytocin receptor (SNP; rs53576) on autonomic and neurohormonal functioning across both resting and psychological stress conditions in a population based sample of older adults. Results revealed that A carrier males showed higher levels of resting sympathetic cardiac control as compared to their G/G counter parts. However, G/G participants displayed significantly higher levels of sympathetic reactivity to psychological stress with G/G males showing the highest levels of sympathetic response to stress. Although no significant effects were detected for heart rate or parasympathetic cardiac control across resting and stress conditions, results revealed that G/G participants generally displayed heightened stroke volume and cardiac output reactivity to the psychological stressor. Furthermore, analysis of diurnal fluctuations in salivary cortisol revealed that G/G participants displayed lower awakening cortisol levels and less variation in salivary cortisol across the day as compared to A carrier individuals.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

An Examination of the Relationship Between Resting Heart Rate Variability and Heart Rate Reactivity to a Mental Arithmetic Stressor

Resting heart rate variability can be an index of sympathetic or parasympathetic dominance, according to the frequency of the variability studied. Sympathetic dominance of this system has been linked to increased risk of cardiovascular disease (CVD). Similarly, rapid and dramatic increases in heart rate reactivity to a stressor task have also been suggested as indicating increased risk of CVD via atherogenesis. Although both of these variables have been related to the development of cardiovascular disease, and both may be related to increased sympathetic activity or parasympathetic withdrawal, most research studies have tended to focus on either variable independently of the other. In order to investigate whether these two indices of stressor reactivity were related in relatively young and healthy subjects, resting heart rate variability data were collected from 80 volunteers for 20 minutes. In addition, heart rate reactivity data were collected during a 2-minute mental arithmetic stressor, which has been previously shown to induce significant increases in heart rate. After classifying subjects according to whether their heart rate variability data were above or below the mean for their gender, heart rate reactivity data were examined via MANOVA to detect significant differences between subject groups. Females showed significant effects, and males showed nonsignificant trends, but these two sets of data were in different directions, suggesting that gender may be a confounding factor in the relationship between heart rate reactivity and heart rate variability.     

Cardiovascular reactivity to mental stress: relationship with menstrual cycle and gender

The purpose of the present study was to determine the fluctuation in cardiovascular reactivity to mental stress during the menstrual cycle by comparing heart rate variability (HRV), and other physiological and psychological data in females with those in males. Cardiovascular reactivity to two mental tasks was measured in 14 females during the follicular and luteal phase of menstruation over two menstrual cycles. The same tasks were subsequently given to a matched pair of males (N=14), at the same intervals as their corresponding females. Heart rate, blood pressure and HRV were used as indices of cardiovascular reactivity. Subjective mental workload was measured at the end of each task. Power spectral analysis of HRV showed that the high frequency (HF) component in HRV decreased more during the luteal phase than the follicular phase. The low frequency (LF) component in HRV and the LF/HF ratio in the luteal phase were significantly higher than that in the follicular phase. The LF component and the LF/HF ratio were significantly lower in females than in males; conversely, the HF component was significantly higher in females than in males. Neither significant effects of menstrual cycle, gender and mental stress nor any significant interactions were found for mental workload. These findings indicate that sympathetic nervous activity in the luteal phase is significantly greater than in the follicular phase whereas parasympathetic nervous activity is predominant in the follicular phase. The results also suggest that predominance of sympathetic nervous activity in males compared with a dominant parasympathetic nervous activity in females.     

Circulating leptin and stress-induced cardiovascular activity in humans

Obesity is associated with an elevated risk of hypertension and cardiovascular disease. The adipocyte hormone leptin, which stimulates energy expenditure in animals by activating the sympathetic nervous system (SNS), is believed to play a role in this association. However, evidence in humans remains sparse. We investigated the relationship between circulating leptin and cardiovascular and inflammatory responses to acute psychological stress in humans. Participants were 32 men and 62 women aged 18-25 years. Cardiovascular activity was assessed using impedance cardiography at baseline, during acute laboratory stress, and during a 45-min recovery period. Plasma cytokines were measured in blood drawn at baseline and 45-min poststress. In women only, baseline plasma leptin was significantly associated with stress-induced changes in heart rate (beta = 0.53, P = 0.006), heart rate variability (HRV) (beta = -0.44, P = 0.015), and cardiac preejection period (PEP) (beta = -0.51, P = 0.004), independent of age, adiposity, and smoking. Women's plasma leptin levels also correlated with stress-induced elevations in the proinflammatory cytokine interleukin-6 (IL-6) (beta = 0.35, P = 0.042). Circulating leptin is an independent predictor of sympathetic cardiovascular activity, parasympathetic withdrawal, and inflammatory responses to stress in women. Because cardiovascular and inflammatory stress responses are predictive of future cardiovascular disease, leptin may be a mechanism mediating the adverse effects of stress and obesity on women's cardiovascular health.     

Cardiovascular alterations and autonomic imbalance in an experimental model of depression

Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms associating depression with such altered cardiovascular parameters are presently unclear. The current study investigated cardiovascular regulation in the chronic mild stress rodent model of depression and examined the specific autonomic nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an essential feature of human depression), along with elevated resting heart rate, decreased heart rate variability, and exaggerated pressor and heart rate responses to air jet stress. Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart. The present findings have implications for the study of pathophysiological links between affective disorders and cardiovascular disease.     

Cardiovascular Response to Interpersonal Provocation and Mental Arithmetic among High and Low Hostile Young Adult Males

To examine the relation between hostility and cardiovascular reactivity to stress, 42 undergraduate men were categorized into high and low hostile groups based on responses to the Cook Medley Hostility Scale. Participants engaged in two laboratory tasks: a Cognitive Task (mental arithmetic) and a Social Task (confrontation role-play). Cardiovascular measures of heart rate and blood pressure were obtained throughout rest and task periods and participants provided ratings of state anger and forgiveness following task completion. Results revealed that low hostile participants exhibited greater systolic blood pressure (SBP) responses to both tasks than high hostile participants (p < .05), but no significant group differences were observed for heart rate or diastolic blood pressure. High hostile men reported greater state anger during resting conditions and less forgiveness following completion of tasks than low-hostile counterparts, but neither of these findings moderated the relation between hostility and SBP reactivity. Higher ratings of forgiveness were associated with lower SBP reactivity. These findings show that hostility is not always associated with exaggerated cardiovascular reactivity to stress, and the influence of various moderating factors should be considered in elucidating this relation.     

Personality and self-motivation during biochemical fatigue

The present study was conducted to determine whether females exhibiting the Type A behavior pattern would exert greater effort and work to higher levels of physiological fatigue in a self-motivated ergometer test. Twenty female subjects, half of them Type A and the other half Type B, were administered an incremental ergometer test to determine their peak oxygen consumption value. On the first experimental session no experimenter encouragement was given to the subjects. Consequently the test measured physical motivation levels. During a second laboratory session, each subject was continuously encouraged by the experimenter to maintain exercising until she was truly incapable of further work. The highest rate of oxygen extraction during this latter session was considered the subject's maximum oxygen consumption (i.e., VO2 max). Type A and B subjects were compared in the nonmotivated testing session (experimental session 1) to their "true" individual capacities (maximum oxygen consumption demonstrated in experimental session 2). ANOVAs indicated no significant differences in self-initiated competitive behavior during a physical stressor.     

The impact of a 6-year comprehensive community trial on the awareness, treatment and control rates of hypertension in Iran: experiences from the Isfahan healthy heart program

Background

Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis.

Methods

Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks.

Results

We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found.

Conclusions

Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect.     

Autonomic nervous system activity in Macaca fascicularis

This study was performed to determine the contributions of the sympathetic and parasympathetic nervous systems to cardiovascular control. Hexamethonium was administered to block the autonomic ganglia, propranolol to block beta adrenergic receptors of the sympathetic nervous system, and methylatropine to block the parasympathetic nervous system. The results of this study indicate high sympathetic tone and low parasympathetic tone in resting Macaca fascicularis. These findings are different from those in man but are similar to other nonhuman primates.     

Interpersonal interaction and cardiovascular response in type A subjects and coronary patients

The present study tested the hypothesis that Type A subjects respond with greater cardiovascular response than Type B subjects during the structured interview used to assess the Type A pattern. Coronary patients (n = 31) and patient controls (n = 33) were subjected to the interview and a history quiz while ECG and blood pressure were monitored. As predicted, Type A relative to Type B subjects evidenced significantly greater increases in both systolic and diastolic blood pressure, which were sustained over the course of the entire 12-15 minute interview. Type A subjects compared with B's also showed significantly greater blood pressure elevations during the quiz. Coronary patients displayed significantly greater Type A attributes than control subjects and tended to show greater blood pressure elevations than controls during the interview. In addition, the quiz induced significant elevations in the blood pressure of coronary patients, but not patient controls, over that displayed during the interview, despite the presence of beta-adrenergic blocking medication. Implications of the findings for coronary-prone behavior and coronary heart disease are discussed.     

The impact of metabolic syndrome and endothelial dysfunction on exercise‐induced cardiovascular changes

Objective:

There is limited information regarding the synergistic or additive effects of metabolic syndrome (MS) and endothelial dysfunction (ED) on cardiovascular disease (CVD). Altered cardiovascular responses to exercise have been shown to predict future cardiovascular events as well as assess autonomic function. The present study evaluated the impact of MS and brachial artery reactivity (a proxy of ED) on peak exercise‐induced cardiovascular changes.

Design and Methods:

Individuals (n = 303) undergoing a standard nuclear medicine exercise stress test were assessed for MS. Participants underwent a Forearm Hyperaemic Reactivity test and were considered to have dysfunctional reactivity if their rate of uptake ratio (RUR) was <3.55. Resting and peak blood pressure (BP) and heart rate (HR) were measured. Reactivity was calculated as the difference between peak and resting measures.

Results:

Analyses, adjusting for age, sex, resting HR, total metabolic equivalents (METs), and a history of major CVD, revealed a main effect of MS (F = 5.51, η² = 0.02, P = 0.02) and RUR (F = 6.69, η² = 0.02, P = 0.01) on HR reactivity, such that patients with MS and/or poor RUR had reduced HR reactivity. There were no interactive effects of RUR and MS. There were no effects of RUR or MS on systolic BP (SBP) or diastolic BP (DBP) reactivity or rate pressure product (RPP) reactivity.

Conclusions:

The presence of decreased HR reactivity among participants with MS or poor brachial artery reactivity, combined with the lack of difference in other exercise‐induced cardiovascular changes, indicates that these patients may have some degree of parasympathetic dysregulation. Further longitudinal studies are needed to understand the long‐term implications of MS and endothelial abnormalities in this context.     

Principal dimensions of the Framingham Type A scale: differential relationships to cardiovascular reactivity and anxiety

The present investigation sought to identify the principal dimensions of the Framingham Type A scale (FTAS) and then to examine their physiological and psychological correlates. A factor analysis of the FTAS items, which was cross-validated, revealed two factors. Items concerning achievement and competitive-striving loaded primarily on the first factor. Scores on a subscale composed of these items (labeled Competitive Drive) were related to systolic blood pressure reactivity during an interpersonal task but were unrelated to anxiety. FTAS items concerning impatient, time urgent, and domineering propensities loaded primarily on the second factor. Scores on a subscale composed of these items (labeled Speed and Impatience) were not related to cardiovascular reactivity during the task but were related to anxiety. Results are discussed in terms of the psychological heterogeneity of the Type A behavior pattern and possible differences between dimensions of the overall Type A pattern and their association with different manifestations of coronary heart disease.     

Vagal modulation of the heart and central hemodynamics during handgrip exercise

Blood pressure and continuous electrocardiogram recordings were obtained from 12 participants during spontaneous breathing (SB1), dynamic handgrip exercise at 20% (HG(20)) of maximal voluntary contraction (MVC), and spontaneous breathing (SB2) and dynamic handgrip exercise at 60% (HG(60)) of MVC. Repeated-measures ANOVAs were used to examine the effects of the exercise conditions on mean arterial pressure (MAP), on mean standard deviation (SDNN), and on the coefficient of variation of R-R intervals. The mean R-R interval responded to exercise in an intensity-dependent manner. SDNN decreased with exercise but was not intensity dependent. Coefficient of variation decreased during HG(20), and MAP increased following HG(60). These data are consistent with the notion that changes in cardiovascular function with low-intensity exercise are primarily mediated by parasympathetic withdrawal, and as exercise intensity increases, additional cardiovascular reactivity is mediated by increased sympathetic outflow. The change in the coefficient of variation from rest to exercise was unique in comparison to the changes in SDNN, and this merits further investigation.     

Effectiveness of emWave Biofeedback in Improving Heart Rate Variability Reactivity to and Recovery from Stress

The current study examined the efficacy of heart rate variability (HRV) biofeedback using emWave, a publicly available biofeedback device, to determine whether training affected physiological tone and stress responses. Twenty-seven individuals aged 18–30 years were randomized to a treatment or no-treatment control group. Treatment participants underwent 4–8 sessions of emWave intervention, and all participants attended pre-treatment and post-treatment assessment sessions during which acute stressors were administered. Physiological data were collected at rest, during stress, and following stress. emWave treatment did not confer changes in tonic measures of HRV or in HRV recovery following stress. However, treatment participants exhibited higher parasympathetic responses (i.e., pNN50) during stress presentations at the post-treatment session than their control counterparts. No treatment effects were evident on self-reported measures of stress, psychological symptoms, or affect. Overall, results from the current study suggest that the emWave may confer some limited treatment effects by increasing HRV during exposure to stress. Additional development and testing of the emWave treatment protocol is necessary before it can be recommended for regular use in clinical settings, including the determination of what physiological changes are clinically meaningful during HRV biofeedback training.     

Control of heart rate variability by cardiac parasympathetic nerve activity during voluntary static exercise in humans with tetraplegia.

Heart rate (HR) is controlled solely by via cardiac parasympathetic outflow in tetraplegic individuals, who lack supraspinal control of sympathetic outflows and circulating catecholamines but have intact vagal pathways. A high-frequency component (HF; at 0.15-0.40 Hz) of the power spectrum of HR variability and its relative value against total power (HF/Total) were assessed using a wavelet transform to identify cardiac parasympathetic outflow. The relative contribution of cardiac parasympathetic and sympathetic outflows to controlling HR was estimated by comparing the HF/Total-HR relationship between age-matched tetraplegic and normal men. Six tetraplegic men with complete cervical spinal cord injury performed static arm exercise at 35% of the maximal voluntary contraction until exhaustion. Although resting cardiac output and arterial blood pressure were lower in tetraplegic than normal subjects, HR, HF, and HF/Total were not statistically different between the two groups. When tetraplegic subjects developed the same force during exercise as normal subjects, HF and HF/Total decreased to 67-90% of the preexercise control and gradually recovered 1.5 min after exercise. The amount and time course of the changes in HF/Total during and after exercise coincided well between both groups. In contrast, the increase in HR at the start of exercise was blunted in tetraplegic compared with normal subjects, and the HR recovery following exercise was also delayed. It is likely that, although the withdrawal response of cardiac parasympathetic outflow is preserved in tetraplegic subjects, sympathetic decentralization impairs the rapid acceleration of HR at the onset of exercise and the rapid deceleration following exercise.     

(In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity

The negative effects of sympathetic overactivity on long-term cardiovascular health are becoming increasingly clear. Moreover, recent work done in animal models of cardiovascular disease suggests that sympathetic tone to the splanchnic vasculature may play an important role in the development and maintenance of these disease states. Work from our laboratory and others led us to hypothesize that a lack of chronic physical activity increases resting and reflex-mediated splanchnic sympathetic nerve activity, possibly through changes occurring in a key brain stem center involved in sympathetic regulation, the rostral ventrolateral medulla (RVLM). To address this hypothesis, we recorded mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA) in a group of active and sedentary animals that had been housed for 10-13 wk with or without running wheels, respectively. In experiments performed under Inactin anesthesia, we tested responses to RVLM microinjections of glutamate, responses to baroreceptor unloading, and vascular reactivity, the latter of which was performed under conditions of autonomic blockade. Sedentary animals exhibited enhanced resting SSNA and MAP, augmented increases in SSNA to RVLM activation and baroreceptor unloading, and enhanced vascular reactivity to α(1)-receptor mediated vasoconstriction. Our results suggest that a sedentary lifestyle increases the risk of cardiovascular disease by augmenting resting and reflex-mediated sympathetic output to the splanchnic circulation and also by increasing vascular sensitivity to adrenergic stimulation. We speculate that regular physical exercise offsets or reverses the progression of these disease processes via similar or disparate mechanisms and warrant further examination into physical (in)activity-induced sympathetic nervous system plasticity.     

Is Baseline Cardiac Autonomic Modulation Related to Performance and Physiological Responses Following a Supramaximal Judo Test?

Little research exists concerning Heart Rate (HR) Variability (HRV) following supramaximal efforts focused on upper-body explosive strength-endurance. Since they may be very demanding, it seems of interest to analyse the relationship among performance, lactate and HR dynamics (i.e. HR, HRV and complexity) following them; as well as to know how baseline cardiac autonomic modulation mediates these relationships. The present study aimed to analyse associations between baseline and post-exercise HR dynamics following a supramaximal Judo test, and their relationship with lactate, in a sample of 22 highly-trained male judoists (20.70±4.56 years). A large association between the increase in HR from resting to exercise condition and performance suggests that individuals exerted a greater sympathetic response to achieve a better performance (Rating of Perceived Exertion: 20; post-exercise peak lactate: 11.57±2.24 mmol/L; 95.76±4.13 % of age-predicted HR_max). Athletes with higher vagal modulation and lower sympathetic modulation at rest achieved both a significant larger ∆HR and a faster post-exercise lactate removal. A enhanced resting parasympathetic modulation might be therefore related to a further usage of autonomic resources and a better immediate metabolic recovery during supramaximal exertions. Furthermore, analyses of variance displayed a persistent increase in α₁ and a decrease in lnRMSSD along the 15 min of recovery, which are indicative of a diminished vagal modulation together with a sympathovagal balance leaning to sympathetic domination. Eventually, time-domain indices (lnRMSSD) showed no lactate correlations, while nonlinear indices (α₁ and lnSaEn) appeared to be moderate to strongly correlated with it, thus pointing to shared mechanisms between neuroautonomic and metabolic regulation.