Music Modulates Autonomic Nervous System Activity in Human Fetuses.

Context: Fetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby. Objective: Aim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability. Methods: Thirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was "Clair de lune" Debussy, played through headphones on the mother's abdomen (CTR: 31927). Results: Music does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037). Conclusion: Music can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition.

Heartbeat-Evoked Cortical Potential during Sleep and Interoceptive Sensitivity: A Matter of Hypnotizability.

Individuals with different hypnotizability display different interoceptive sensitivity/awareness (IS) and accuracy (IA), likely sustained by morphofunctional differences in interoception-related brain regions and, thus, possibly also observable during sleep. We investigated the heartbeat-evoked cortical potential amplitude (HEP) during sleep, its association with IS, and the role of hypnotizability in such association. We performed a retrospective analysis of polysomnographic recordings of 39 healthy volunteers. Participants completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), measuring IS and IA, and underwent hypnotic assessment via the Stanford Hypnotic Susceptibility Scale, form A. The amplitude of the early and late HEP components was computed at EEG frontal and central sites. In both regions, the early HEP component was larger in N3 than in N2 and REM, with no difference between N2 and REM. Greater HEP amplitude at frontal than at central sites was found for the late HEP component. HEP amplitudes were not influenced by the autonomic state assessed by heart rate variability in the frequency and time domains. We report for the first time a positive correlation between the central late HEP component and MAIA dimensions, which became non-significant after removing the effects of hypnotizability. Our findings indicate that hypnotizability sustains the correlation between IS and HEP amplitude during sleep.

Geometric Features of the Pial Arteriolar Networks in Spontaneous Hypertensive Rats: A Crucial Aspect Underlying the Blood Flow Regulation.

BACKGROUND: Several studies indicate that hypertension causes major changes in the structure of the vessel wall by affecting the regulation of blood supply to the tissues. Recently, it has been observed that capillary blood flow is also considerably influenced by the structural arrangement of the microvascular networks that undergo rarefaction (reduction of the perfused vessel number). Therefore, this study aimed to assess the geometric arrangements of the pial arteriolar networks and the arteriolar rhythmic diameter changes in spontaneously hypertensive rats (SHRs). METHODS: Fluorescence microscopy was utilized to observe in vivo the pial microcirculation through a closed cranial window. Pial arterioles were classified according to Strahler's method. The arteriolar rhythmic diameter changes were evaluated by a generalization short-time Fourier transform. RESULT: Young SHRs showed four orders of vessels while the adult ones only three orders. The diameter, length, and branching number obeyed Horton's law; therefore, the vessels were distributed in a fractal manner. Larger arterioles showed more asymmetrical branches than did the smaller ones in young SHRs, while in adult SHRs smaller vessels presented asymmetrical branchings. In adult SHRs, there was a significant reduction in the cross-sectional area compared with the young SHRs: this implies an increase in peripheral resistance. Young and adult age-matched normotensive rats did not show significant alterations in the geometric arteriolar arrangement with advancing age, both had four orders of arteriolar vessels, and the peripheral resistance did not change significantly. Conversely, the frequency components evaluated in arteriolar rhythmic diameter changes of young and adult SHRs showed significant differences because of a reduction in the frequency components related to endothelial activity detected in adult SHRs. CONCLUSION: In conclusion, hypertension progressively causes changes in the microarchitecture of the arteriolar networks with a smaller number of vessels and consequent reduced conductivity, characteristic of rarefaction. This was accompanied by a reduction in the formation and release of independent and dependent - endothelial nitric oxide components regulating arterial vasomotion.

A feasibility study on non-invasive fetal ECG to evaluate prenatal autonomic nervous system activity.

BACKGROUND: Maturity of the autonomic nervous system (ANS) is of paramount importance for fetal adaptation to extrauterine life and for early neurological development. Markers of ANS maturity, such as electrophysiological heart rate parameters, are of interest as tools to determine prenatal fetal maturity. The available technology, fetal magnetocardiography is expensive and not suitable for clinical use. Detection of fetal electrocardiographic signals using traditional ECG leads on the maternal abdomen may be brought to the bedside, but is technically challenging. Our group has recently developed an innovative system consisting of a standard ECG with external leads applied on the maternal abdomen coupled with a software that extracts the fetal heart signal from the maternal noise. OBJECTIVE: To validate the use of this innovative non-invasive system to detect fetal ECG (fECG) and its ability to detect changes in electrophysiological fetal cardiac parameters associated with ANS maturation. STUDY DESIGN: we recruited 50 pregnant women between 24 and 41 weeks and they received non-invasive recording of fECG. RESULTS: fECG was measurable at all gestational ages. Fetal heart rate variability (RR interval) and other associated parameters, such as low and high frequency increased with gestational age, particularly up to the 31st week. CONCLUSIONS: This study shows that non-invasive fECG is feasible throughout a broad range of gestational ages and allows detecting electrophysiological parameters of the fetal heart that may be used a surrogate of ANS maturity. Technological implementation of this system and its further exploitation may generate new tool to estimate fetal maturity.

Effects of Mandibular Extension on Pial Arteriolar Diameter Changes in Glucocorticoid-Induced Hypertensive Rats.

Previously, in normotensive rats, it has been observed that a repetitive sub-maximal mouth opening (mandibular extension, ME) obtained by placing a home-made U-shaped dilator between the superior and inferior dental arches of the rat caused modulation of pial arteriolar tone. The present study was aimed to characterize pial microcirculation in two different cortical brain regions and to assess the hemodynamic effects of a single or double ME on pial arteriolar rhythmic diameter changes in rats rendered hypertensive by dexamethasone administrations. Cranial windows were prepared on parietal and frontal region. Pial arterioles were classified by Strahler method in five orders by in vivo fluorescence microscopy technique associated with a computerized system that permits off-line measurements of arteriolar diameter changes. Two 10 min ME at 10 min interval were applied; then the animals were monitored for further 240 min. Dexamethasone-treated rats exhibited a marked arterial rarefaction and asymmetry of bifurcation in the pial microvascular networks more evident in the frontal region. Starting from ME1, in both cortical areas, the arterioles dilated, and the vasodilation became significant compared to baseline after ME2 for the entire observation period. The spectral analysis carried out on order 2 arteriolar diameter change tracings, showed that double ME increased the spectral density of the frequency components related to endothelial, neuronal and myogenic activities in both the cortical regions studied. In conclusion, double ME has a generalized effect in the cortical areas by restoring the physiological vasomotion of the pial arterioles that was severely impaired by the experimentally hypertension.

Patient-specific seizure prediction based on heart rate variability and recurrence quantification analysis.

Epilepsy is often associated with modifications in autonomic nervous system, which usually precede the onset of seizures of several minutes. Thus, there is a great interest in identifying these modifications enough time in advance to prevent a dangerous effect and to intervene. In addition, these changes can be a risk factor for epileptic patients and can increase the possibility of death. Notably autonomic changes associated to seizures are highly depended of seizure type, localization and lateralization. The aim of this study was to develop a patient-specific approach to predict seizures using electrocardiogram (ECG) features. Specifically, from the RR series, both time and frequency variables and features obtained by the recurrence quantification analysis were used. The algorithm was applied in a dataset of 15 patients with 38 different types of seizures. A feature selection step, was used to identify those features that were more significant in discriminating preictal and interictal phases. A preictal interval of 15 minutes was selected. A support vector machine (SVM) classifier was then built to classify preictal and interictal phases. First, a classifier was set up to classify preictal and interictal segments of each patient and an average sensibility of 89.06% was obtained, with a number of false positive per hour (FP/h) of 0.41. Then, in those patients who had at least 3 seizures, a double-cross-validation approach was used to predict unseen seizures on the basis of a training on previous ones. The results were quite variable according to seizure type, achieving the best performance in patients with more stereotypical seizure. The results of the proposed approach show that it is feasible to predict seizure in advance, considering patient-specific, and possible seizure specific, characteristics.

HYPNOTIZABILITY AND PAIN MODULATION: A Body-Mind Perspective.

The study investigated whether the cardiac activity and cognitive-emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the presence and absence of suggestions for analgesia. Results showed that heart rate increased abruptly at the beginning of nociceptive stimulation in all participants. Then, only in highs heart rate decreased for the entire duration of hand immersion. During stimulation with suggestions of analgesia, pain threshold negatively correlated with heart rate. BIS/BAS activity partially accounted for the observed hypnotizability-related differences in the relation between cardiac interoception and pain experience.

Heart Rate Variability During a Joint Attention Task in Toddlers With Autism Spectrum Disorders.

Background: Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders featuring early impairments in social domain, with autonomic nervous system (ANS) unbalance possibly representing a useful marker for such disturbances. Impairments in joint attention (JA) are one of the earliest markers of social deficits in ASD. In this study, we assessed the feasibility of using wearable technologies for characterizing the ANS response in ASD toddlers during the presentation of JA stimuli. Methods: Twenty ASD toddlers and 20 age- and gender-matched typically developed (TD) children were recorded at baseline and during a JA task through an unobtrusive chest strap for electrocardiography (ECG). Specific algorithms for feature extraction, including Heart Rate (HR), Standard Deviation of the Normal-to-Normal Intervals (SDNN), Coefficient of Variation (CV), pNN10 as well as low frequency (LF) and high frequency (HF), were applied to the ECG signal and a statistical comparison between the two groups was performed. Results: As regards the single phases, SDNN (p = 0.04) and CV (p = 0.021) were increased in ASD at baseline together with increased LF absolute power (p = 0.034). Moreover, CV remained higher in ASD during the task (p = 0.03). Considering the phase and group interaction, LF increased from baseline to task in TD group (p = 0.04) while it decreased in the ASD group (p = 0.04). Conclusions: The results of this study indicate the feasibility of characterizing the ANS response in ASD toddlers through a minimally obtrusive tool. Our analysis showed an increased SDNN and CV in toddlers with ASD particularly at baseline compared to TD and lower LF during the task. These findings could suggest the possibility of using the proposed approach for evaluating physiological correlates of JA response in young children with ASD.

Low-Frequency Components in Rat Pial Arteriolar Rhythmic Diameter Changes.

This study aimed to analyze the frequency components present in spontaneous rhythmic diameter changes in rat pial arterioles. Pial microcirculation was visualized by fluorescence microscopy. Rhythmic luminal variations were evaluated via computer-assisted methods. Spectral analysis was carried out on 30-min recordings under baseline conditions and after administration of acetylcholine (Ach), papaverine (Pap), Nω-nitro-L-arginine (L-NNA) prior to Ach, indomethacin (INDO), INDO prior to Ach, charybdotoxin and apamin, and charybdotoxin and apamin prior to Ach. Under baseline conditions all arteriolar orders showed 3 frequency components in the ranges of 0.0095-0.02, 0.02-0.06, and 0.06-0.2 Hz, another 2 in the ranges of 0.2-2.0 and 2.5-4.5 Hz, and another ultra-low-frequency component in the range of 0.001-0.0095 Hz. Ach caused a significant increase in the spectral density of the frequency components in the range of 0.001-0.2 Hz. Pap was able to slightly increase spectral density in the ranges of 0.001-0.0095 and 0.0095-0.02 Hz. L-NNA mainly attenuated arteriolar responses to Ach. INDO prior to Ach did not affect the endothelial response to Ach. Charybdotoxin and apamin, suggested as endothelium-derived hyperpolarizing factor inhibitors, reduced spectral density in the range of 0.001-0.0095 Hz before and after Ach administration. In conclusion, regulation of the blood flow distribution is due to several mechanisms, one of which is affected by charibdotoxin and apamin, modulating the vascular tone.

Repeated Mandibular Extension in Rat: A Procedure to Modulate the Cerebral Arteriolar Tone.

Previous data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity.

A Combined Independent Source Separation and Quality Index Optimization Method for Fetal ECG Extraction from Abdominal Maternal Leads.

The non-invasive fetal electrocardiogram (fECG) technique has recently received considerable interest in monitoring fetal health. The aim of our paper is to propose a novel fECG algorithm based on the combination of the criteria of independent source separation and of a quality index optimization (ICAQIO-based). The algorithm was compared with two methods applying the two different criteria independently-the ICA-based and the QIO-based methods-which were previously developed by our group. All three methods were tested on the recently implemented Fetal ECG Synthetic Database (FECGSYNDB). Moreover, the performance of the algorithm was tested on real data from the PhysioNet fetal ECG Challenge 2013 Database. The proposed combined method outperformed the other two algorithms on the FECGSYNDB (ICAQIO-based: 98.78%, QIO-based: 97.77%, ICA-based: 97.61%). Significant differences were obtained in particular in the conditions when uterine contractions and maternal and fetal ectopic beats occurred. On the real data, all three methods obtained very high performances, with the QIO-based method proving slightly better than the other two (ICAQIO-based: 99.38%, QIO-based: 99.76%, ICA-based: 99.37%). The findings from this study suggest that the proposed method could potentially be applied as a novel algorithm for accurate extraction of fECG, especially in critical recording conditions.

Pain modulation as a function of hypnotizability: Diffuse noxious inhibitory control induced by cold pressor test vs explicit suggestions of analgesia.

The aim of the present study was to compare the effects of explicit suggestions of analgesia and of the activation of the Diffuse Noxious Inhibitory Control (DNIC) by cold pressor test on pain perception and heart rate in healthy participants with high (highs, N=18), low (lows, N=18) and intermediate scores of hypnotizability (mediums, N=15) out of hypnosis. Pain reports and the stimulus-locked heart rate changes induced by electrical nociceptive stimulation of the left hand were studied in the absence of concomitant stimuli (Control), during suggestions of analgesia (SUGG, glove analgesia) and during cold pressor test used as a conditioning stimulus to the right hand (DNIC, water temperature=10-12°C) in the REAL session. Participants were submitted also to a SHAM session in which the DNIC water temperature was 30°C and the suggestions for analgesia were substituted with weather forecast information. Both suggestions and DNIC reduced pain significantly in all subjects; however, the percentage of reduction was significantly larger in highs (pain intensity=55% of the control condition) than in mediums (70%) and lows (80%) independently of the REAL/SHAM session and of the specific pain manipulation. Heart rate was not modulated consistently with pain experience. Findings indicate that both suggestions and DNIC influence pain experience as a function of hypnotizability and suggest that both sensory and cognitive mechanisms co-operate in DNIC induced analgesia.

A new method for QRS complex detection in multichannel ECG: Application to self-monitoring of fetal health.

This paper proposes a new approach for QRS complex detection in multichannel ECG and presents its application to fetal QRS (fQRS) detection in signals acquired from maternal abdominal leads. The method exploits the characteristics of pseudo-periodicity and time shape of QRS, it consists of devising a quality index (QI) which synthesizes these characteristics and of finding the linear combination of the acquired ECGs, which maximizes this QI. In the application for fQRS detection two QIs are devised, one QI (mQI) for maternal ECG (mECG) and one QI (fQI) for fetal ECG (fECG). The method is completely unsupervised and based on the following steps: signal pre-processing; maternal QRS-enhanced signal extraction by finding the linear combination that maximize the mQI; detection of maternal QRSs; mECG component approximation and canceling by weighted Singular Value Decomposition (SVD); fQRS-enhanced signal extraction by finding the linear combination that maximize the fQI and fQRS detection. The proposed method was compared with our previously developed Independent Component Analysis (ICA) based method as well as with simple mECG canceling and simple ICA methods. The comparison was carried out by evaluating the performances of the procedures in fQRS detection. The new method outperformed the results of the other approaches on the annotated open set of the Computing in Cardiology Challenge 2013 database. The proposed method seems to be promising for its implementation on portable device and for use in self-monitoring of fetal health in pregnant women.

Blink reflex in subjects with different hypnotizability: New findings for an old debate.

Hypnotizability is associated with attentional characteristics whose neurophysiological bases are still under debate. Aim of the study was the assessment of possible hypnotizability-related differences in blink reflex (BR) which has a nociceptive component, is sensitive to attentional-emotional traits and states and is modulated by the brain dopamine content. In 10 high (highs) and 10 low hypnotizable participants (lows) BR was induced by electrical nociceptive stimulation of the right supraorbital nerve in the absence (noW) and in the presence of a visual cue preceding the electrical stimulation by 0.1ms (W01) and by 1ms (W1). The studied variables were: the amplitude of BR components (R1, R2, R3), the amplitude of the quick change (TO) of heart rate ("turbulence") induced by stimulation and its recovery slope (TS), the role of the Behavioral Inhibition/Activation System (BIS/BAS) in the variability BR and cardiac turbulence. Repeated measures ANOVA did not show any significant difference between highs and lows in blink reflex. TO indicated stimulation related HR increase in highs and decrease in lows, TS was larger in highs. BIS and BAS accounted for the warning effects on the BR amplitude and modulated the hypnotizability and warning effects on TO and TS. Findings do not support dopamine based hypnotizability-related attentional abilities. In contrast, they indicate that hypnotizability modulates the short-lasting cardiac response to electrical nociceptive stimulation.

Paradoxical response to an emotional task: trait characteristics and heart-rate dynamics.

The present study evaluated the heart-rate dynamics of subjects reporting decreased (responders) or paradoxically increased relaxation (nonresponders) at the end of a threatening movie. Heart-rate dynamics were characterized by indices extracted through recurrence quantification analysis (RQA) and detrended fluctuation analysis (DFA). These indices were studied as a function of a few individual characteristics: hypnotizability, gender, absorption, anxiety, and the activity of the behavioral inhibition and activation systems (BIS/BAS). Results showed that (a) the subjective experience of responsiveness is associated with the activity of the behavioral inhibition system and (b) a few RQA and DFA indices are able to capture the influence of cognitive-emotional traits, including hypnotizability, on the responsiveness to the threatening task.

Cognitive modulation of psychophysical, respiratory and autonomic responses to cold pressor test.

In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability.

Pain-inducing imagery as a function of hypnotisability and of the activity of Gray's Behavioral Inhibition/Activation Systems.

The aim of the study was to test the efficacy of pain imagery as a function of hypnotisability and of the activity of Behavioral Inhibition/Activation Systems. Questionnaires of imagery abilities (Betts) for the visual, cutaneous and organic modalities, absorption in cognitive tasks (TAS), proneness to inhibit stressful/painful experience/seek out positive experiences (BIS BAS), trait anxiety (STAI-Y2) and psychological well-being (PWB) were administered to 21 subjects with high hypnotisability (highs) and 21 subjects with low hypnotisability (lows). Self-reports of pain intensity and of neutral tactile perception were collected during imagery of nociceptive (Pain) and neutral tactile stimulation (NT). ECG and skin conductance were recorded. Highs exhibited greater imagery abilities, absorption, Behavioral Inhibition System Activity and psychological well-being with respect to lows. They reported lower scores of pain intensity than of tactile perception, while in lows Pain and NT scores did not differ. However, controlling for BAS, but not for BIS, revealed differences in the efficacy of pain imagery between highs and lows. Heart rate decreased in both tasks and groups; heart rate variability and skin conductance did not change significantly during imageries. Our findings suggest that the Behavioral Inhibition/Activation Systems interact with imagery abilities reducing the efficacy of pain imagery and prompt investigation of possible similar interactions in the modulation of physically induced experimental pain and of chronic pain in the general population.

Hypnotizability modulates the cardiovascular correlates of subjective relaxation.

Mean values and the spectral variability of heart rate (HRV), blood pressure, and skin blood flow were studied in high and low hypnotizable subjects during simple relaxation. Similar subjective relaxation was reported by highs and lows. A parasympathetic prevalence (indicated by a higher High-Frequency component of HRV and a lower High/Low-Frequency ratio) and lower renin-angiotensin activity (indicated by a lower Very-Low-Frequency component of HRV) could be attributed to highs with respect to lows. Hypnotizability did not affect blood pressure and its variability and modulated the skin blood flow across the session only in lows. The findings confirm that relaxation cannot be defined solely on cardiovascular parameters and also indicate that hypnotizability modulates cardiovascular activity during simple relaxation and suggest it may have a protective role against cardiovascular disease.

Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients.

BACKGROUND: Essential hypertension is characterized by both increased oxidative stress and sympathetic traffic. Experimental studies have shown that reactive oxygen species can modulate autonomic activity. OBJECTIVE: The aim of this study was to determine whether acute administration of the antioxidant vitamin C modifies sympathetic nerve activity in essential hypertension. DESIGN: Thirty-two untreated patients with essential hypertension and 20 normotensive subjects received vitamin C (3 g intravenously in 5 min) or vehicle. Heart rate, noninvasive beat-to-beat blood pressure, and muscle sympathetic nerve activity (microneurography) were monitored at baseline and up to 20 min after the infusion. Spectral analysis of RR interval variability and spontaneous baroreflex sensitivity were also computed. RESULTS: Vitamin C infusion significantly lowered blood pressure in hypertensive patients but not in normotensive subjects (maximal changes in systolic blood pressure: -4.9 ± 10.1 compared with -0.7 ± 4.0 mm Hg, respectively; P < 0.05). Moreover, muscle sympathetic nerve activity was significantly reduced after vitamin C infusion in hypertensive patients (from 53.3 ± 12.2 to 47.4 ± 11.5 bursts/100 heart beats; P < 0.01) but not in healthy subjects (from 42.0 ± 10.1 to 42.7 ± 11.8 bursts/100 heart beats; NS). On the contrary, in 16 hypertensive patients, sodium nitroprusside in equidepressor doses induced a significant increase in muscle sympathetic nerve activity compared with vitamin C (+10.0 ± 6.9 bursts/100 heart beats). Sympathovagal balance and spontaneous baroreflex sensitivity were restored during vitamin C infusion in hypertensive subjects. CONCLUSIONS: These results indicate that acute administration of vitamin C is able to reduce cardiovascular adrenergic drive in hypertensive patients, which suggests that oxidative stress is involved in the regulation of sympathetic activity in essential hypertension.