Peripheral Sympathetic Responses Research Articles

Combining electrodermal activity analysis and dynamic causal modeling to investigate the visual-odor multimodal integration during face perception

Objective. This study presents a novel methodological approach for incorporating information related to the peripheral sympathetic response into the investigation of neural dynamics. Particularly, we explore how hedonic contextual olfactory stimuli influence the processing of neutral faces in terms of sympathetic response, event-related potentials and effective connectivity analysis. The objective is to investigate how the emotional valence of odors influences the cortical connectivity underlying face processing and the role of face-induced sympathetic arousal in this visual-olfactory multimodal integration. Approach. To this aim, we combine electrodermal activity (EDA) analysis and dynamic causal modeling to examine changes in cortico-cortical interactions. Results. The results reveal that stimuli arising sympathetic EDA responses are associated with a more negative N170 amplitude, which may be a marker of heightened arousal in response to faces. Hedonic odors, on the other hand, lead to a more negative N1 component and a reduced the vertex positive potential when they are unpleasant or pleasant. Concerning connectivity, unpleasant odors strengthen the forward connection from the inferior temporal gyrus (ITG) to the middle temporal gyrus, which is involved in processing changeable facial features. Conversely, the occurrence of sympathetic responses after a stimulus is correlated with an inhibition of this same connection and an enhancement of the backward connection from ITG to the fusiform face gyrus. Significance. These findings suggest that unpleasant odors may enhance the interpretation of emotional expressions and mental states, while faces capable of eliciting sympathetic arousal prioritize identity processing.

Video-based sympathetic arousal assessment via peripheral blood flow estimation.

Electrodermal activity (EDA) is considered a standard marker of sympathetic activity. However, traditional EDA measurement requires electrodes in steady contact with the skin. Can sympathetic arousal be measured using only an optical sensor, such as an RGB camera? This paper presents a novel approach to infer sympathetic arousal by measuring the peripheral blood flow on the face or hand optically. We contribute a self-recorded dataset of 21 participants, comprising synchronized videos of participants' faces and palms and gold-standard EDA and photoplethysmography (PPG) signals. Our results show that we can measure peripheral sympathetic responses that closely correlate with the ground truth EDA. We obtain median correlations of 0.57 to 0.63 between our inferred signals and the ground truth EDA using only videos of the participants' palms or foreheads or PPG signals from the foreheads or fingers. We also show that sympathetic arousal is best inferred from the forehead, finger, or palm.

Orexin facilitates the hypoxic ventilatory response via the activation of corticotropin-releasing hormone neurons that project to the nucleus of the solitary tract

The paraventricular nucleus of the hypothalamus (PVN) contributes significantly to the peripheral chemoreflex-mediated respiratory and sympathetic responses to hypoxia, in part via reciprocal interactions with nucleus of the solitary tract (nTS). Previously we showed that orexin neurons in the perifornical hypothalamus are activated by hypoxia and facilitate the hypoxic ventilatory response (HVR) in the active phase of the circadian cycle . The neural circuitry through which orexin facilitates the HVR is unknown. Orexin receptors (OxR) are expressed in the PVN, and we recently showed that OxR blockade reduced the activation of both corticotropin-releasing hormone neurons in the PVN as well as nTS neurons. In addition, hypoxia activated orexin neurons projecting to the PVN, but not those projecting to nTS. Here we further explored the hypothesis that orexin facilitates the HVR and arterial blood pressure (ABP) response to hypoxia via the activation of nTS-projecting CRH neurons, and that specific OxR1 knockdown in the PVN would reduce the HVR. To test these hypotheses, we nanoinjected fluorescent retrobeads bilaterally into the nTS to label nTS-projecting neurons. Rats were then exposed to hypoxia (2hrs at 11% O2 during the active phase) following injection of either suvorexant (OxR antagonist; 20 mg/kg i.p.; n=4), or vehicle (DMSO; n=4). Using immunohistochemistry (IHC) we then quantified the number of activated (i.e., Fos-immunoreactive; IR) nTS-projecting CRH neurons. In separate groups of rats we nanoinjected shRNA to knockdown Ox1R expression specifically in the PVN (n=8). PVN of control rats was nanoinjected with scrambled RNA (scRNA; n=3) or aCSF (n=2). Three weeks later, rats were exposed to graded hypoxia (from 21% to 10% inspired O2) over 3-5 minutes to assess the acute HVR and ABP response to different levels of hypoxia. OxR blockade reduced the number of Fos-IR, nTS-projecting CRH neurons by ~32% (drug: p<0.0001). Images confirmed successful targeting of shRNA to PVN, and OxR1 knockdown (by ~50%) was confirmed in subsets of samples by Western Blot and IHC. Ox1R knockdown specifically in the PVN had no effect on resting ventilation, but significantly reduced the HVR (main effect: p=0.02; 22% decrease in VE/VCO2 at 13% O2), due to a reduction in the respiratory frequency response to hypoxia (main effect: p=0.004; 38 breath/min decrease at 13% O2). Ox1R knockdown also decreased ABP (~5 mmHg at all O2 levels; main effect: p=0.0015), but not its response to hypoxia. These data suggest that orexin neurons facilitate the HVR via OxR1 Grants: 5R01HL098602 (EH, DK), 5R01HL136710 (KC) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Diminished autonomic nervous system responses to acoustic startle in progressive supranuclear palsy (S8.003)

<h3>Objective:</h3> To examine possible autonomic changes associated with progressive supranuclear palsy in response to a strong, unanticipated stimulus. <h3>Background:</h3> Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that causes serious problems in eye movements, walking, and balance, and is also often associated with cognitive, emotional, and behavioral changes. In other movement disorders such as Parkinson’s disease, similar symptoms have often been associated with changes in autonomic nervous system (ANS) functioning. Despite this, previous studies have rarely examined ANS functioning in PSP.. In the present study, we determined whether ANS responses to an emotionally provocative stimulus were altered in PSP. We tested the hypothesis that ANS responses to an unanticipated aversive auditory stimulus (i.e., a brief, loud burst of white noise) designed to induce a startle response would differ between patients with PSP compared to healthy controls (HC). <h3>Design/Methods:</h3> Participants included 33 PSP patients and 38 HC. Participants sat still for a 60 second baseline and heard a brief (100-ms) loud (115-dB) burst of white noise without warning. Continuous measures of cardiac interbeat intervals (IBI; decreases in IBI correspond to increases in heart rate) and skin conductance levels (SCL) were obtained throughout the task. <h3>Results:</h3> Compared to HC, PSP patients showed significantly less decrease in IBI (i.e., less increase in heart rate) and less increase in SCL from baseline during the 10 seconds after stimulus onset. <h3>Conclusions:</h3> Less decrease in IBI and less increase in SCL in the face of a strong external stimulus suggests a diminished sympathetic nervous system response. In light of previous research suggesting that peripheral sympathetic responses are relatively preserved in the setting of orthostatic postural testing in PSP, we suspect this relates to a brainstem degeneration in a pontine circuit that is critical for startle reflexes during emotional challenges. <b>Disclosure:</b> The institution of Dr. Pressman has received research support from Premiere. Dr. Pressman has received personal compensation in the range of $100,000-$499,999 for serving as a Associate Professor with University of Colorado School of Medicine. The institution of Dr. Chen has received research support from National Institute on Aging. Ms. Bullard has nothing to disclose. The institution of Dr. Rankin has received research support from Marcus Foundation. Robert Levenson has nothing to disclose.

Glucose infusion suppresses acute restraint stress-induced peripheral and central sympathetic responses in rats.

Acute restraint stress (RS) induces sympathetic activation such as elevating plasma catecholamines, resulting in increase in blood glucose. We aimed to investigate whether glucose infusion affects the RS-induced sympathetic responses. Plasma catecholamines were measured by high-performance liquid chromatography with electrochemical detection. Blood glucose levels were measured with a glucometer and a glucose assay kit. Cardiac parameters were measured by echocardiographic and hemodynamic analysis. Prostanoid levels in the paraventricular nucleus of hypothalamus (PVN) microdialysates were measured by liquid chromatography-ion trap tandem mass spectrometry analysis. RS significantly increased plasma noradrenaline and adrenaline. Intravenous infusion of a 5% glucose solution significantly attenuated the RS-induced elevation of plasma adrenaline but did not alter the plasma noradrenaline. Glucose administration during RS suppressed the progression of cardiac impairment by attenuating the decline rates in left ventricular diastolic, end-diastolic volume, stroke volume, fractional shortening, and ejection fraction. Both Intravenous and intracerebroventricular infusion of glucose solution significantly attenuated the RS-induced elevation of thromboxane B2 (TxB2) (a metabolite of TxA2) levels in the PVN but did not alter prostaglandin E2 levels in the PVN. Our results demonstrate that glucose infusion suppresses RS-induced elevation of plasma adrenaline and left ventricular dysfunction. In the brain, glucose infusion suppresses RS-induced production of TxA2 in the PVN.

Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man

An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual’s BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography.

Peripheral Nerve Conduction And Sympathetic Skin Response Are Reliable Methods to Detect Diabetic Cardiac Autonomic Neuropathy.

AimThis study aimed to investigate the role of nerve conduction studies (NCS) and sympathetic skin response (SSR) in evaluating diabetic cardiac autonomic neuropathy (DCAN).MethodsDCAN was diagnosed using the Ewing test combined with heart rate variability analysis. NCS and SSR were assessed by electrophysiological methods. The association between NCS/SSR and DCAN was assessed via multivariate regression and receiver-operating characteristic analyses.ResultsThe amplitude and conduction velocity of the motor/sensory nerve were found to be significantly lower in the DCAN+ group (all P < 0.05). A lower amplitude of peroneal nerve motor fiber was found to be associated with increased odds for DCAN (OR 2.77, P < 0.05). The SSR amplitude was lower while the SSR latency was longer in the DCAN+ group than in the DCAN– group. The receiver-operating characteristic analysis revealed that the optimal cutoff points of upper/lower limb amplitude of SSR to indicate DCAN were 1.40 mV (sensitivity, 61.9%; specificity, 66.3%, P < 0.001) and 0.85 mV (sensitivity, 66.7%; specificity, 68.5%, P < 0.001), respectively. The optimal cutoff points of upper/lower limb latency to indicate DCAN were 1.40 s (sensitivity, 61.9%; specificity, 62%, P < 0.05) and 1.81 s (sensitivity, 69.0%; specificity, 52.2%, P < 0.05), respectively.ConclusionsNCS and SSR are reliable methods to detect DCAN. Abnormality in the peroneal nerve (motor nerve) is crucial in predicting DCAN. SSR may help predict DCAN.

Vagal deficiency in Patients with Chronic Heart Failure: A series of 31 cases

Heart failure (HF) is a major problem of public health. Autonomic Nervous System dysfunction is involved in the physiopathology of heart failure. The aim of our study is to determine the prevalence of vagal deficiency in patients with chronic heart failure Our serie is a descriptive and analytical retrospective study and has included 31 patients with chronic heart failure admitted in Cardiology Centre, Mohammed V Military Hospital of Rabat, Morocco. All of them had cardiovascular autonomic testing including Deep Breathing, Hand grip, Mental stress and orthostatic tests. The mean age was 64,7 ± 9,8 years with male predominance (81%). They have more than three cardio vascular risk factors dominated by Hypertension (84%), smoking (71%), Diabetes (45%) with an average HbA1 C at 8.8%. The mean ejection fraction was ˂ 40%.The baseline mean Heart Rate was 88.37 ± 16.52 bpm, the mean systolic blood pressure was 130 ± 22 mmHg and Diastolic blood pressure was 74 ± 10 mmHg. Vagal Deficiency (VD) was found in 88% of patients in all different tests, alpha (α)peripheral sympathetic response was 10.54 ± 1.34% and high α and β central sympathetic response respectively at 21.46 ± 1.13% and 18.02 ± 1.2%. This study demonstrated a significant vagal deficiency response in patients with Chronic Heart Failure. Redressing sympathovagal balance can be feasible and should be advantageous, through medical treatment, cardiac Rehabilitation already proven cornerstone of HF treatment and vagal stimulation as a new approach with promising results.

Non-invasive Vagal Nerve Stimulation Paired with Stress Exposure in Posttraumatic Stress Disorder (PTSD)

Non-invasive Vagal Nerve Stimulation (nVNS) is a new device that has promise for the study of vagal nerve physiology as well as clinical application in patients with psychiatric disorders. Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can follow exposure to psychological trauma and is associated with intrusive memories, nightmares, avoidance, and problems with sleep and concentration. Exposure to reminders of the traumatic event can activate PTSD symptoms. We and others have shown changes in brain circuits in PTSD, including decreased medial prefrontal and increased amygdala function, as well as increased peripheral sympathetic and inflammatory responses, impaired autonomic tone, and an increased risk for coronary heart disease. In the current study, subjects with a history of exposure to psychological trauma undergo both trauma-specific and neutral stressors (math stress, public speaking) paired with nVNS or sham stimulation to the neck in conjunction with High Resolution Positron Emission Tomographic (HR-PET) with radiolabelled water imaging of the brain and measurement of stress biomarkers (e.g., inflammatory markers, cortisol, norepinephrine), as well as assessment of cardiovascular and autonomic parameters using wearable sensory devices. Pre-ejection Period (PEP) (the time interval between electrical depolarization of the left ventricle and the opening of the aortic valve) shortening is a marker of increased sympathetic tone, as is seen with stress. Other outcomes include peripheral vasoconstriction and rate pressure product (RPP). Preliminary findings show decreased inflammatory markers, blocked shortening of PEP, and increased medial prefrontal (anterior cingulate) function with nVNS paired to traumatic scripts but not sham controls. These findings suggest that nVNS has effects on both central and peripheral stress response systems in humans that may counteract the effects of stress. This research has implications for new treatments involving electrical stimulation in PTSD.

HIGH SYMPATHETIC RESPONSE AND PHENOBARBITAL IN PRIMARY HYPERTENSIVE PATIENTS

Objective: The literature showed that the high sympathetic activity can be considered as a cardiovascular risk factor. This phenomenon has been well found in primary hypertensive patients (PHP). The purpose of this study was to see if phenobarbital in small doses (10 mg) is able to decrease the sympathetic hyperactivity in primary hypertensive patients (PHP) using cardiovascular autonomic reflexes before and after treatment.Design and method: This prospective study was conducted on a total of 123 primary hypertensive patients (PHP) in whom we noted a high central and/or peripheral sympathetic response diagnosed by mental stress and orthostatic tests. Inclusion criteria: All primary hypertensive patients who had shown a sympathetic hyperactivity were included in this study. Exclusion criteria. The patients with an abnormal electrocardiogram, severe arterial hypertension, secondary or complicated hypertension or having over-sensitiveness to the molecule were excluded from this study. This is a prospective study comparing two cardiac autonomic evaluations: pre and post-therapeutic, carried out in the unit of exploration of the autonomic nervous system, service of cardiology “A” at the University hospital Ibn Sina. A written consent form was obtained from each patient before the tests. Statistical analysis: Group comparisons were carried out by independent samples Student's t-test for interval variables and the khi squart test for categorical variables, with 95% confidence intervals (CIs) calculated where appropriate. P significant if < 0.05. All analyses were performed using SPSS, version 15.0 (SPSS Inc., Chicago, Il). Results: Table 1: Alpha peripheral sympathetic response (alpha SP) obtained on hand grip test. Alpha central sympathetic response (alpha SC), beta central sympathetic response (beta SC) obtained during mental stress, and alpha peripheral adrenergic sympathetic (alpha PAS). Parameters were measured before and after treatment by phenobarbital, and expressed as mean ± SE; P is significative if < 5%. Conclusions: In hypertensive patients, use of Phenobarbital (10 mg) showed a significant decrease of the sympathetic activity.

Evidence for Pressure-Independent Sympathetic Modulation of Central Pulse Wave Velocity.

BackgroundWhether the sympathetic nervous system can directly alter central aortic stiffness remains controversial, mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure.Methods and ResultsTo address this limitation, we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation. Blood pressure and carotid‐femoral aortic pulse wave velocity (cf‐PWV) were measured in 32 healthy participants (24±2 years; women: n=15) before and during 12‐minute applications of low‐level lower body negative pressure; −7 mm Hg) and lower body positive pressure; +7 mm Hg), applied in a random order. Fibular nerve microneurography was used to collect muscle sympathetic nerve activity (MSNA) in a subset (n=8) to confirm peripheral sympathetic responses. During lower body negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05); MSNA burst frequency (+15%; P=0.007), total MSNA (+44%; P=0.006), and cf‐PWV (∆+0.3±0.2 m/s; P<0.001) increased. In total, 28 (88%) of participants observed an increase in cf‐PWV greater than the baseline typical error of measurement. During lower body positive pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05), though blood pressure increased (P<0.05) and pulse pressure decreased (P=0.01); MSNA burst frequency (−4%; P=0.37), total MSNA (−7%; P=0.89), and cf‐PWV (∆0.0±0.2 m/s; P=0.68) were not statistically different.ConclusionsThese findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV in young participants independent of a change in distending or pulsatile blood pressure or heart rate.

Neurologic Complications in HPV Vaccination

A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus vaccination. The average incubation period after the first dose of the vaccine was 5.47 ± 5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the feet, limb pain, and weakness. The skin temperature of the girls with limb symptoms was slightly lower in the fingers and moderately lower in the toes. Digital plethysmograms revealed a reduced peak of the waves, especially in the toes. Limb symptoms of the affected girls were compatible with the diagnostic criteria for complex regional pain syndrome. The Schellong test identified a significant number of patients with orthostatic hypotension and a few with postural orthostatic tachycardia syndrome. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the patients was psychosomatic disease. Recently, delayed manifestation of cognitive dysfunction in the post-vaccinated girls has attracted attention. The symptoms include memory loss and difficulty in reading textbooks and/or calculation.

Peripheral Sympathetic Nerve Dysfunction in Adolescent Japanese Girls Following Immunization with the Human Papillomavirus Vaccine

To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine. During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study. The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6 °C) and a moderate decrease in the toes (27.1±3.7 °C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school.

Imaging Facial Signs of Neurophysiological Responses

In the present paper, we introduce an integrated framework for detecting peripheral sympathetic responses through purely imaging means. The measurements are performed on three facial areas of sympathetic importance, that is, periorbital, supraorbital, and maxillary. To the best of our knowledge, this is the first time that the sympathetic importance of the maxillary area is analyzed. Because the imaging measurements are thermal in nature and are composed of multiple components of variable frequency (i.e., blood flow, sweat gland activation, and breathing), we chose wavelets as the image analysis framework. The measurements also carry substantial noise due to imperfections in tissue tracking and segmentation. The image analysis is grounded on galvanic skin response (GSR) signals, which are still considered the golden standard in peripheral neurophysiological and psychophysiological studies. The experimental results show that monitoring of the facial channels yields similar detecting power to GSR's. However, detailed quantification of the responses, although feasible in GSR through appropriate modeling, is quite difficult in the facial channels for the moment. Further improvements in facial tissue tracking and segmentation are bound to overcome this limitation. This paper opens a new research area that leads to unobtrusive screening technologies in neurophysiology and psychophysiology.

Chronic lithium administration enhances noradrenergic responses to intravenous administration of the alpha2 antagonist idazoxan in healthy volunteers.

The acute and chronic effects of lithium carbonate administration at therapeutic blood levels on peripheral noradrenergic activity and sympathetic responses to alpha2 adrenoceptor blockade were examined in 10 medically and psychiatrically healthy volunteers. Supine resting levels of plasma norepinephrine and the increases in norepinephrine following intravenous infusion of 200 microg/kg of idazoxan, a selective alpha2 adrenoceptor antagonist, were determined before lithium (Li+) administration and after 5 days and after 4 weeks of daily Li+ treatment. Chronic Li+ treatment significantly increased mean resting plasma norepinephrine levels by 53.6%. The noradrenergic responses to infusions of idazoxan were slightly enhanced after 5 days of Li+ administration and significantly increased following 4 weeks of Li+ treatment. The possibility that Li+ produces functional alpha2 subsensitivity causing enhanced peripheral noradrenergic activity in humans is supported by the findings of increased mean resting plasma norepinephrine and increased response to idazoxan following chronic Li+ administration. Alteration of regulatory mechanisms in the noradrenergic system may be relevant to understanding the clinical effects of Li+ in manic-depressive illness.

Nitroglycerin-induced activation of monoaminergic transmission in the rat.

When administered to migraine patients, nitroglycerin induces a spontaneous-like migraine attack, with a latency of several hours. Nitroglycerin acts directly and/or indirectly on the central nervous system, through the release of nitric oxide (NO). Systemic administration of the drug to the rat causes neuronal activation in selected subcortical areas, particularly in monoaminergic nuclei of the brainstem. In this study, we sought to investigate whether this activation correlates with changes in monoaminergic neurotransmission. For this purpose, we evaluated the tissue levels of catecholamines and serotonin in the hypothalamus, mesencephalon, pons and medulla of rats treated with systemic nitroglycerin or vehicle, at different time points (1, 2 and 4 h). We also evaluated the peripheral sympathetic response to the drug by measuring the concentrations of plasma catecholamines. Nitroglycerin caused an early (1 h) increase in cerebral (pons) and plasma levels of norepinephrine, followed by a delayed (4 h) decrease in medullary and pontine levels of serotonin. The initial noradrenergic activation may reflect the autonomic response to the rapid cardiovascular effects of the drug, while the delayed response may result from the interaction of nitroglycerin-released NO and 5-HT in central areas devoted to the modulation of nociception. These data might therefore help to clarify the mechanisms underlying the delayed migraine attack observed in migraine sufferers after systemic administration of nitroglycerin.

Cardiovascular indices of peripheral and central sympathetic activation.

A number of sympathetic nervous system (SNS) parameters have been used in cardiovascular psychophysiology. This study aimed to describe the pattern and redundancy of a set of SNS parameters during peripherally induced changes of cardiac sympathetic activation and reflex modulation of central SNS control. Preejection period (PEP) was assessed as a marker of peripheral sympathetic activation. Low-frequency blood pressure variability (BPV) was assessed as an estimate of central SNS control. Peripheral beta-sympathetic stimulation and blockade were achieved with epinephrine and esmolol hydrochloride (beta1-blockade), respectively. Changes in central SNS output were induced by loading and unloading arterial baroreceptors with norepinephrine and nitroprusside sodium, respectively. This single-blinded, crossover study in 24 healthy men also included two placebo control periods. PEP was derived from impedance cardiography and adjusted individually for heart rate. BPV was calculated by power spectral analyses of beat-to-beat heart rate and systolic blood pressure (Finapres system) data. PEP decreased during epinephrine infusion (-40.1 +/- 3.8 ms, p <.0001) and increased during esmolol infusion (+6.6 +/- 3.5 ms, p =.05). PEP was shortened after central SNS activation by nitroprusside (-16.8 +/- 2.9 ms, p < 0.0001). Systolic BPV in the low-frequency range (0.07-0.14 Hz, Mayer waves) increased during nitroprusside infusion (+0.44 +/- 0.19 ln mm Hg(2), p =.03) and decreased during norepinephrine infusion (-0.67 +/- 0.13 ln mm Hg(2), p < 0.0001). Low-frequency BPV did not change significantly during epinephrine or esmolol infusion. Our data provide empirical evidence of separable peripheral and central sympathetic response components. The combined report of low-frequency BPV and PEP gives distinct information on both central SNS control and the level of sympathetic cardiac activation achieved.

Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat

We investigated the central and peripheral sympathetic responses to intermittent dehydration in rats. The norepinephrine (NE) turnover, a biochemical index correlated with noradrenergic neuronal activity, was measured. The modification of blood pressure was also determined by telemetry during the different cycles of dehydration. Dehydration caused a decrease of NE turnover in A2, A5 and A6 nuclei and in peripheral organs. The vasopressinergic level of dehydrated rats decreased in hypophysis and hypothalamus, and increased in plasma. A repeated gradual increase of arterial blood pressure during the first three days of dehydration, followed by a sudden drop when the rats were rehydrated on the fourth day was observed. In conclusion, our study revealed an increase in blood pressure and in central sympathetic activity during dehydration.

Effects of Acute and Chronic Starvation on Central and Peripheral Noradrenaline Turnover, Blood Pressure and Heart Rate in the Rat

SUMMARYWhen faced with stress, an organism calls upon several mechanisms to maintain biological homeostasis. The cardiovascular system is the first to respond usually with an increase in arterial pressure and tachycardia. Therefore we investigated the central and peripheral sympathetic responses to acute and chronic starvation in Wistar rats. The noradrenaline (NA) turnover rate was determined in different catecholaminergic nuclei (A1, A2, A5, A6) as well as the arterial blood pressure and heart rate modifications. During acute starvation (3 days of starvation), the NA turnover was increased in the A1 and rostral A2 nuclei as well as in ventricles and kidneys and decreased in the A6 nucleus. During chronic starvation (4 consecutive cycles of 3 days of starvation plus 1 day of feeding), the NA turnover was increased in the A5 and caudal A2 nuclei as well as in ventricles and atria and decreased in the A1 nucleus and kidneys. The arterial blood pressure revealed a gradual decrease during the first 3 days of fasting but the heart rate was not modified. We conclude that starvation should be considered as an unusual state of stress because of the absence of locus coeruleus response (A6 nucleus) despite its well‐defined role in stress reactions. One of the manifestations of these central and peripheral noradrenergic changes is the change in blood pressure during the starvation‐feeding cycles.

Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat.

Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia. For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia. In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were made in the cortex. Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.