Cross system autonomic balance and regulation: Associations with depression and anxiety symptoms

The autonomic nervous system (ANS) has demonstrated utility for identifying alterations in emotion processing associated with common psychopathology, including depression and anxiety. To date though the majority of this ANS research has several limitations. Most studies have examined parasympathetic and sympathetic branches separately, requiring activity in the other branch be inferred. This is problematic as each branch may function independently. Composite indices such as cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) which examine the relative input between respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP) should provide more comprehensive measures of autonomic functioning and thus stronger predictors of psychopathology. However, the sympathetic branch is driven by multiple neurotransmitter systems, thus PEP does not necessarily reflect overall SNS arousal. We propose two new metrics for assessing ANS functioning associated with psychopathology: parasympathetic effects on cardiac control (RSA) relative to sympathetic effects on the eccrine system (electrodermal activity, EDA), which we term cross-system autonomic balance (CSAB) and regulation (CSAR). Eighty-five women (18–37) completed a baseline physiological assessment with parasympathetic (RSA) and sympathetic indices (PEP, EDA), along with self-reported depressive and anxiety symptoms. Lower CSAB, indicating sympathetic dominance driven by cholinergic neurotransmission, was associated with higher depressive and anxiety symptoms. Lower CAB indicating sympathetic dominance driven by beta-adrenergic neurotransmission was associated specifically with depressive symptoms. CSAB was a more robust index than RSA. Results support the utility of assessing multiple composite ANS indices for identifying physiological substrates of alterations in emotion regulation associated with internalizing disorders.     

Specific subtypes of nicotinic cholinergic receptors involved in sympathetic and parasympathetic cardiovascular responses

Various subtypes of nicotinic cholinergic receptors are expressed in autonomic ganglia. The distinct functional roles of these receptors in autonomic ganglionic transmission to different target organs remain to be elucidated. In this study, we tested the sympathetic and parasympathetic cardiovascular responses to nicotinic agonist and antagonists in urethane-anesthetized mice. Intravenous injection with a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, induced a brief but pronounced decrease in heart rate, followed by significant increases in heart rate and arterial blood pressure. The bradycardic response was blocked by atropine whereas the pressor response was blocked by prazosine, confirming those responses were parasympathetic and sympathetic activities, respectively. The sympathetic response was blocked by methyllycaconitine citrate, a selective α7 nicotinic cholinergic receptor (nAchR) antagonist. The parasympathetic response was blocked by a selective α4β2 nAchR antagonist, dihydro-β-erythroidine hydrobromide. Moreover, injection with a selective α4β2 nAchR agonist, RJR2403 oxalate, induced a pronounced parasympathetic response with a smaller sympathetic response. Collectively, these data show that activations of α4β2 nAchRs elicits a parasympathetic cardiovascular response and activation of α7 nAchRs elicits a sympathetic cardiovascular response. These data suggest that specific subtypes of nicotinic receptors at the level of the ganglia may play distinct roles in mediating sympathetic or parasympathetic activation.     

Usefulness of cardiac parasympathetic index in CPAP‐treated patients with obstructive sleep apnea: A preliminary study

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full‐night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability‐polysomnographic study included 16 never‐treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full‐night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high‐frequency and low‐frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea–hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single‐night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea–hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice.     

Respiratory and cardiac rhythms as windows to central and autonomic biobehavioral regulation: selection of window frames, keeping the panes clean and viewing the neural topography.

Respiratory and cardiovascular processes figure importantly in biobehavioral regulation. Various cardiac and respiratory measures may, furthermore, index the activity of relatively distinct central and autonomic mechanisms. In this regard, I consider ventilatory indices of central drive and timing of respiration, and rhythmic cardiac-interval fluctuations as reflections of parasympathetic and sympathetic cardiac influences. Particular emphasis is placed upon the phenomenon of respiratory sinus arrhythmia (RSA). A number of conceptual and methodological questions are addressed concerning quantification and inference. Among others, these include the following issues: (1) What is the evidence that the three cardiac periodicities slower than heart rate reflect distinct autonomic mechanisms? (2) Does RSA reflect tonic or phasic parasympathetic regulation of heart rate? (3) Do specific quantification procedures for measuring these rhythms provide superior estimates? (4) What are some potential pitfalls for quantification and inference.     

Oxytocin increases autonomic cardiac control: moderation by loneliness

The current study examined the role of perceived social isolation in moderating the effects of oxytocin on cardiac autonomic control in humans. Intranasal administration of 20 IU oxytocin resulted in a significant increase in autonomic (parasympathetic and sympathetic) cardiac control. Specifically, oxytocin increased high frequency heart rate variability, a relatively pure measure of parasympathetic cardiac control, and decreased pre-ejection period, a well-validated marker of enhanced sympathetic cardiac control. Derived metrics of autonomic co-activity and reciprocity revealed that oxytocin significantly increased overall autonomic cardiac control. Furthermore, the effects of oxytocin on cardiac autonomic control were significantly associated with loneliness ratings. Higher levels of loneliness were associated with diminished parasympathetic cardiac reactivity to intranasal oxytocin. The effects of OT on autonomic cardiac control were independent of any effects on circulating pro-inflammatory cytokine or stress hormone levels. Thus, lonely individuals may be less responsive to the salubrious effects of oxytocin on cardiovascular responsivity.     

Myocardial Dysfunction and Pathology Associated with Environmental Stress in Squirrel Monkey: Effect of Vagotomy and Propranolol

The influence of autonomic innervation on stress-induced cardiomyopathy and heart rate changes was analyzed by selective removal of parasympathetic and sympathetic myocardial inputs. Squirrel monkeys with bilateral cervical vagotomy or β-adrenergic receptors blocked by propranolol were studied in shock stress and restraint situations. Because propranolol reduced stress-induced lesions and tachycardia, enhanced sympathetic β-receptor activity was considered responsible for these effects in intact monkeys. No role for increased parasympathetic activity in myocardial pathology was indicated. Enhanced sympathetic activity was also implicated by lesions and tachycardia of vagotomy monkeys. However, vagotomy alone induced myocardial pathology and confounded the effects of shock stress. Stress-induced cardiac arrest in both vagotomy and propranolol monkeys was observed. An imbalance of either autonomic input was suggested to be responsible for this dysfunction. Thus, autonomic innervation was involved in stress-induced cardiomyopathy and heart rate changes.     

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.     

The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies

This article evaluates the suitability of low frequency (LF) heart rate variability (HRV) as an index of sympathetic cardiac control and the LF/high frequency (HF) ratio as an index of autonomic balance. It includes a comprehensive literature review and a reanalysis of some previous studies on autonomic cardiovascular regulation. The following sources of evidence are addressed: effects of manipulations affecting sympathetic and vagal activity on HRV, predictions of group differences in cardiac autonomic regulation from HRV, relationships between HRV and other cardiac parameters, and the theoretical and mathematical bases of the concept of autonomic balance. Available data challenge the interpretation of the LF and LF/HF ratio as indices of sympathetic cardiac control and autonomic balance, respectively, and suggest that the HRV power spectrum, including its LF component, is mainly determined by the parasympathetic system.     

Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo

Somatic noxious stimulation can evoke profound cardiovascular responses by altering activity in the autonomic nervous system. This noxious stimulation attenuates the cardiac vagal baroreflex, a key cardiovascular homeostatic reflex. This attenuation is mediated via NK₁ receptors expressed on GABAergic interneurones within the nucleus of the solitary tract (NTS). We have investigated the effect of noxious stimulation and exogenous substance P (SP) on the sympathetic component of the baroreflex. We recorded from the sympathetic chain in a decerebrate, artificially perfused rat preparation. Noxious hindlimb pinch was without effect on the sympathetic baroreflex although the cardiac vagal baroreflex gain was decreased (56 %, P < 0.01). Bilateral NTS microinjection of SP (500 fmol) produced a similar selective attenuation of the cardiac vagal baroreflex gain (62 %, P < 0.005) without effect on the sympathetic baroreflex. Recordings from the cardiac sympathetic and vagal nerves confirmed the selectivity of the SP inhibition. Control experiments using a GABA_A receptor agonist, isoguvacine, indicated that both components of the baroreflex (parasympathetic and sympathetic) could be blocked from the NTS injection site. The NTS microinjection of a NK₁ antagonist (CP-99,994) in vivo attenuated the tachycardic response to hindlimb pinch. Our data suggest that noxious pinch releases SP within the NTS to selectively attenuate the cardiac vagal, but not the sympathetic, component of the baroreflex. This selective withdrawal of the cardiac vagal baroreflex seems to underlie the pinch-evoked tachycardia seen in vivo . Further, these findings confirm that baroreflex sympathetic and parasympathetic pathways diverge, and can be independently controlled, within the NTS.     

Emotional reactivity modulates autonomic responses to an acoustic challenge in quail

Emotional reactivity modulates autonomic responses to an acoustic challenge in quail. Physio Behav 00(0) 000-000, 2006. This study investigated the relationship between emotional reactivity and behavioral and autonomic responses to an acoustic stimulus in quail. It was hypothesized that birds with high emotional reactivity would have higher motor inhibition combined with higher sympathetic activation than birds with low emotional reactivity. Two experiments were performed. The first looked for correlations between emotional reactivity, evaluated by a tonic immobility test, and motor and Heart Rate Variability in relation to an acoustic stimulus. The second experiment compared the motor and autonomic responses to the acoustic stimulus of quail selected on either long (LTI) or short (STI) duration of tonic immobility. The first experiment showed that the acoustic stimulation induced motor inhibition and cardiac activation. Correlations were found between tonic immobility duration and both autonomic activity before stimulation and sympathovagal balance after stimulation. In the second experiment, LTI quail showed strong sympathetic activation, whereas STI quail showed parasympathetic and sympathetic activation. The activation of the parasympathetic system induced by the noise in STI quail can be explained by the predominance of this system at rest in this line. In conclusion, both the basal autonomic activity and the autonomic responses differed according to the emotional reactivity, and changes in autonomic activity appear to be related to the genetic selection process.     

Cortical and affective regulation of autonomic coordination

Although anatomical research clearly demonstrates the ability of the sympathetic and parasympathetic branches of the autonomic nervous system to independently influence cardiac function, little research has examined whether coordinated activation is typical or whether the extent of autonomic coordination is situationally dependent. This study examines the extent of coordination between sympathetic (cardiac pre-ejection period: PEP) and parasympathetic (respiratory sinus arrhythmia: RSA) influences on the cardiac function to determine whether coordination is a trait-like between-person characteristic or a state-varying within-person phenomenon, and if so, whether variability in autonomic coordination is modulated by cognitive (P3b amplitude) or affective state. Kindergarten-aged children (n = 257) completed a go/no-go task administered in blocks designed to induce affective states through the delivery of reward (Blocks 1 and 3) and frustration (Block 2). Results from multilevel models that allowed for the simultaneous examination of between-person and within-person associations in the repeated measures data suggested that (a) children with higher overall RSA also tended to have higher overall PEP; (b) at within-person level, RSA and PEP tended to be reciprocally coordinated; but that (c) when frustration invokes cognitive disengagement, coordination between parasympathetic and sympathetic systems demonstrate compensatory coordination. These findings highlight the extent to which the coordination of autonomic systems is a dynamic state-like phenomenon rather than a trait-like individual differences characteristic.     

Stress cardiovascular/autonomic interactions in mice

Studies evaluated the role of the autonomic nervous system in the cardiovascular response to stress using radiotelemetric blood pressure (BP) recording coupled with autoregressive spectral analysis. Conscious male C57/BL6 mice with carotid arterial telemetric catheters were exposed to acute episodes of shaker stress before and after administration of cholinergic, beta1-adrenergic and alpha1-adrenergic receptor antagonists. Pulse interval (PI) and systolic arterial pressure (SAP) were analyzed for variance and the low frequency (LF: 0.1-1.0 Hz) and high frequency (HF: 1-5 Hz) spectral components. Stress (5 min) increased BP and heart rate (HR) as well as PI and SAP variability. PI variance increased from 41+/-6 to 75+/-14 ms2 while SAP variance increased from 25+/-5 to 55+/-9 mm Hg2. Autonomic blockade had specific effects on stress-induced changes in PI and SAP and their respective variability. Atropine reduced the tachycardia and abolished the increase in PI variance and its LF component. Data documents that in mice the cholinergic system is fundamental for the maintenance of HR variability. Atropine had no effects on the BP responses, either the increase in SAP or the variance associated with stress. Atenolol blocked the increase in PI and SAP variability induced by stress. Prazosin reduced the tachycardia produced by stress and blocked the increase in PI (only LF) and SAP variability. Using quantitative spectral analysis of telemetrically collected BP data in mice along with pharmacological antagonism, we were able to accurately determine the role of autonomic input in the mediation of the stress response. Data verify the role of sympathetic/parasympathetic balance in stress-induced changes in HR, BP and indices of variance.     

Person perception and autonomic nervous system response: The costs and benefits of possessing a high social status

This research was designed to investigate the relationship between sympathetic and parasympathetic autonomic nervous system (ANS) responses to the perception of social targets varying in social status. Participants varying in subjective financial status were presented with faces assigned with either a low, average, or high financial status. Electrocardiographic and impedance cardiography signals were recorded and measures of sympathetic (pre-ejection period; PEP) and parasympathetic (high frequency heart rate variability; HF HRV) cardiac control were derived. These measures associated with the presentation of each face condition were examined in relation to the subjective status of the perceivers. Participants with high subjective financial status showed reduced sympathetic activity when viewing low- and medium-status targets as compared to high-status targets, and lower parasympathetic response when viewing high- and medium-status targets relative to low-status targets.     

Alteration of cardiac autonomic functions in patients with major depression: a study using heart rate variability measures

BACKGROUND: Depression is associated with greater cardiac morbidity and mortality. One of the contributory factors for this may be altered cardiac autonomic activity in depression. However, cardiac autonomic involvement in depression remains controversial because of methodological issues. In this study, alteration of cardiac autonomic functions was studied in drug-naive patients with major depression without co-morbidity. Heart rate variability, a sensitive measure of neurocardiac autonomic regulation was used in addition to conventional methods of measuring cardiac autonomic functions. METHODS: We recruited 40 patients suffering from major depression, diagnosed based on DSM-IV-TR criteria. Their cardiac autonomic functions were measured using both conventional and heart rate variability measures. These were compared with those of age- and gender-matched healthy controls. RESULTS: Patients with major depression showed significantly lesser Valsalva ratio, maximum/minimum ratio and greater sympathovagal balance than healthy controls indicating decreased parasympathetic and increased sympathetic activity. CONCLUSIONS: Depression is associated with alteration of cardiac autonomic tone towards decreased parasympathetic activity and an increased sympathetic activity. It is possible that a common neurobiological dysfunction contributes to both depression and cardiac autonomic changes in the illness.     

Characterization of ouabain-induced noradrenaline and acetylcholine release from in situ cardiac autonomic nerve endings

Aim: Although ouabain modulates autonomic nerve ending function, it is uncertain whether ouabain‐induced releasing mechanism differs between in vivo sympathetic and parasympathetic nerve endings. Using cardiac dialysis, we examined how ouabain induces neurotransmitter release from autonomic nerve ending. Methods: Dialysis probe was implanted in left ventricle, and dialysate noradrenaline (NA) or acetylcholine (ACh) levels in the anaesthetized cats were measured as indices of neurotransmitter release from post‐ganglionic autonomic nerve endings. Results: Locally applied ouabain (100 μm ) increased in dialysate NA or ACh levels. The ouabain‐induced increases in NA levels remained unaffected by cardiac sympathetic denervation and tetrodotoxin (Na⁺ channel blocker, TTX), but the ouabain‐induced increases in ACh levels were attenuated by TTX. The ouabain‐induced increases in NA levels were suppressed by pretreatment with desipramine (NA transport blocker) and augmented by reserpine (vesicle NA transport blocker). In contrast, the ouabain‐induced increases in ACh levels remained unaffected by pretreatment with hemicholinium‐3 (choline transport blocker) but suppressed by vesamicol (vesicle ACh transport blocker). The ouabain‐induced increases in NA levels were suppressed by pretreatment with ω‐conotoxin GVIA (N‐type Ca²⁺ channel blocker), verapamil (L‐type Ca²⁺ channel blocker) and TMB‐8 (intracellular Ca²⁺ antagonist). The ouabain‐induced increases in ACh levels were suppressed by pretreatment with ω‐conotoxin MVIIC (P/Q‐type Ca²⁺ channel blocker), and TMB‐8. Conclusions: Ouabain‐induced NA release is attributable to the mechanisms of regional exocytosis and/or carrier‐mediated outward transport of NA, from stored NA vesicle and/or axoplasma, respectively, while the ouabain‐induced ACh release is attributable to the mechanism of exocytosis, which is triggered by regional depolarization. At both sympathetic and parasympathetic nerve endings, the regional exocytosis is because of opening of calcium channels and intracellular calcium mobilization.     

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher‐order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high‐frequency heart rate variability, HF‐HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high‐risk women. HF‐HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within‐person fluctuations in WM performance throughout the task concurrently with HF‐HRV and PEP, as well as between‐person differences as a function of resting HF‐HRV and PEP levels. Results indicate that resting PEP moderated the association between HF‐HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow‐up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation.     

Autonomic space and psychophysiological response

Contemporary findings reveal that autonomic control of dually innervated target organs cannot adequately be viewed as a continuum extending from parasympathetic to sympathetic dominance. Rather, a two-dimensional autonomic space, bounded by sympathetic and parasympathetic axes, is the minimal representation necessary to characterize the multiple modes of autonomic control. We have previously considered the theoretical implications of this view and have developed quantitative conceptual models of the formal properties of autonomic space and its translation into target organ effects. In the present paper, we further develop this perspective by an empirical instantiation of the quantitative autonomic space model for the control of cardiac chronotropy in the rat. We show that this model (a) provides a more comprehensive characterization of cardiac response than simple measures of end-organ state, (b) permits a parsing of the multiple transformations underlying psychophysiological responses, (c) illuminates and subsumes psychophysiological principles, such as the Law of Initial Values, (d) reveals an interpretive advantage of expressing cardiac chronotropy in heart period rather than heart rate, and (e) has fundamental implications for the direction and interpretation of a broad range of psychophysiological studies.     

Cholinergic and adrenergic innervation of microvessels of the serous membranes

The morphological substrate of dual (sympathetic and parasympathetic) innervation of the microblood-vessels was studied in the serous membranes of the cat. By the use of histochemical methods to demonstrate cholinergic (Koelle-Gomori) and adrenergic (Falck-Hillarp) nerve structures the architectonics of both components of the vasomotor innervation was described in the pericardium, pleura, and peritoneum. Adrenergic structures were more numerous than cholinergic in corresponding segments of the arterial system. The autonomic innervation of the terminal arterioles and capillaries was inconstant in character and was essentially confined to single synaptic contacts arising along the course of the adrenergic and cholinergic terminals. In the veins, including the post capillary venules and small collecting veins, the autonomic innervation (both adrenergic and cholinergic) was exceptionally poorly developed and sometimes impossible to detect.     

Autonomic control of pacemaker activity in the atrioventricular junction of the dog

A stable atrioventricular (AV) junctional rhythm was induced in open-chest, anesthetized dogs by injecting pentobarbital into the sinus node artery. A factorial experimental design was used to quantify the changes in AV junctional rate as a function of the frequency of cardiac sympathetic and parasympathetic stimulation. The AV junctional pacemaker cells were more responsive to autonomic neural stimulation, but the vagal-sympathetic interactions were less pronounced than had previously been observed for the SA nodal pacemaker cells. In a group of seven animals, sympathetic stimulation at a frequency of 1.4 Hz increased the AV junctional rate by 102% from a control rate of 54 beats/min. In the same animals, vagal stimulation at a frequency of 8.4 Hz reduced the AV junctional rate by 56%. In three other animals, the AV junction was even more responsive; equivalent chronotropic effects were achieved with stimulation frequencies that were only about one-third of those cited above. There was a moderate, but significant, autonomic interaction: in the group of seven animals, the positive chronotropic effect of sympathetic stimulation at 1.4 Hz was 72% greater at the low level (0 Hz) than at the high level (8.4 Hz) of vagal activity.     

Cardiac autonomic profile during rest and working memory load in essential hypotensive women

To our knowledge, no previous study has provided reliable data supporting a different modulation of the Neurovegetative system in essential hypotension. Our purpose was to provide, in essential hypotensive women compared to normotensives, evidence of a distinct sympathetic and parasympathetic cardiac control. Cardiovascular and autonomic indexes derived by impedance cardiography (heart rate, HR; pre-ejection period, PEP), photoplethysmographic technique (blood pressure, BP) and heart rate variability analysis (high and low frequencies power, HF and LF) were continuously collected during rest and mental stress condition. Hypotensives, compared to normotensives, exhibited prolonged PEP (low sympathetic tone) and elevated HF (high vagal involvement) during rest. In addition, they showed cardiovascular (reduced increases in BP and HR) and sympathetic (lower reductions of PEP) hypo-reactivity to the task. Furthermore, a lower sympathetic reactivity in hypotensives was associated to a poorer task performance. Essential hypotension was characterized by a low sympathetic and high parasympathetic tone. In addition, a reduced sympathetic nervous system reactivity suggests the main role of the Neurovegetative system in mediating the relationship between blood pressure and cognitive performance in hypotensives.