Sympathetic Discharge Research Articles

Sympathetic single axonal discharge after spinal cord injury in humans: activity at rest and after bladder stimulation

Clinical experimental mechanistic study. (1) To determine in three spinal cord-injured patients whether individual muscle sympathetic nerve fibres below the level of the spinal lesion display spontaneous activity. (2) To determine in these patients if individual sympathetic vasoconstrictor fibres show a prolonged discharge following a bladder stimulus. University hospital in Gothenburg, Sweden. Microneurographic recordings of action potentials from individual muscle nerve sympathetic fibres in a peroneal nerve. Recordings of skin blood flow and electrodermal responses in a foot. In all patients, there was sparse ongoing spontaneous impulse traffic in individual sympathetic fibres. Brisk mechanical pressure over the urinary bladder evoked a varying number of action potentials in individual fibres, but the activity was brief and did not continue after the end of the evoked multiunit burst. Prolonged discharges in individual sympathetic fibres are unlikely to contribute to a long duration of blood pressure increases induced by brief bladder stimuli.

Relationship of Heart Rate Variability to Sleepiness in Patients with Obstructive Sleep Apnea with and without Heart Failure

Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Dexmedetomidine and regulation of splenic sympathetic nerve discharge

Recent lines of inquiry indicate that sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

Differentiated Baroreflex Modulation of Sympathetic Nerve Activity During Deep Brain Stimulation in Humans

Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.

Comparative study of clonidine versus lignocaine for attenuation of hemodynamic responses during laparoscopic hysterectomy

Background: Hemodynamic changes due to reflex sympathetic discharge are of great concern in laparoscopic surgeries. Aim: To compare hemodynamic changes following premedication with lignocaine or clonidine during laparoscopic hysterectomy. Subjects and Methods: This prospective cross‑sectional randomized double blinded controlled trial was conducted one year in a tertiary care hospital in West Bengal. After taking institutional ethical clearance and consent of patients, hundred subjects of ASA Grade I and II undergoing elective laparoscopic hysterectomy were included in the study. Patients were allocated into two groups. Group A received clonidine and Group B received lignocaine. Baseline clinical parameters were recorded. Patients received clonidine or lignocaine as a bolus over a period of 15 minutes before induction and as continuous intravenous infusion throughout the surgical procedure. The dose of clonidine was 2.25 µg/kg bolus and 0.9 µg/kg/hr infusion while that of lignocaine was 1.5 mg/kg bolus and 0.6 mg/kg/hr infusion. Patients were given 1 µg/kg of fentanyl citrate intravenously. Following inductionwith intravenous propofol, endotracheal intubation was facilitated by atracurium. Anaesthesia was maintained by nitrous oxideIN and oxygen and along with propofol infusion. Muscle relaxation was achieved by intermittent bolus doses of atracurium. The patients were mechanically ventilated to keep EtCO 2 between 35 and 40 mm Hg. Residual neuromuscular block was reversed by an appropriate dose of neostigmine and glycopyrrolate. All patients were shifted to PACU/POCU. Ramsay Sedation Score was assessed. Data was analyzed using SPSS version 16. Results: In comparison to group B, attenuation of heart rate, Systolic blood pressure, diastolic blood pressures were significantly more in group A. There was no difference in sedation score between the two groups. Conclusion: In an attempt to attenuate both the effects of layngoscopy and insufflations with carbon dioxide in laparoscopic surgery infusions of clonidine and lignocaine were run all through the procedures in the present study and it was found that use of clonidine and lignocaine attenuated the haemodynamic responses. However clonidine being found to be more effective.

Effect Of Theophylline On Blood Pressure Of Normotensive Cats Pre-Administered With Adrenaline

The effect of various volumes of theophylline (Aminophylline) (4mg/kg) on the blood pressure of normotensive cats pre-administered with adrenaline was determined. The results obtained revealed that theophylline showed a potentiating effect (p<0.05)oncatecolamines (adrenaline (10µg/ml) in elevating the systolic, diastolic and mean arterial blood pressure of the normotensive cats. Although,theophylline alone caused an increase (p<0.05) in the diastolic and mean arterial blood pressure which may be due to the increase sympathetic discharge by theophylline. The antagonistic test carried out reveals the attenuatic effect (p<0.05) of the calcium channel blocker (nifedipine 2mg/ml) on the combination (adrenaline and theophylline). Theophylline posesses a potentiating effect on catecholamine in determining it effect on blood pressure of normotensive cats and it was inhibited by L-type calcium channel blocker (nifedipine).

Association of hypertension status and cardiovascular risks with sympathovagal imbalance in first degree relatives of type 2 diabetics.

As reports show cardiovascular (CV) risks in first-degree relatives (FDR) of type2 diabetics, and autonomic imbalance predisposing to CV risks, in the present study we have assessed the contribution of sympathovagal imbalance (SVI) to CV risks in these subjects. Body mass index (BMI), waist-to-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in FDR of type2 diabetics (study group, n=293) and in subjects with no family history of diabetes (control group, n=405). The ratio of low-frequency (LF) to high-frequency (HF) power of HRV (LF-HF), a sensitive marker of SVI, was significantly increased (P<0.001) in the study group compared with the control group. The SVI in the study group was due to concomitant sympathetic activation (increased LF) and vagal inhibition (decreased HF). In the study group, the LF-HF ratio was significantly correlated with BMI, WHR, BHR, BP and RPP. Multiple regression analysis showed an independent contribution of LF-HF to hypertension status (P=0.000), and bivariate logistic regression showed significant prediction (odds ratio 2.16, confidence interval 1.130-5.115) of LF-HF to increased RPP, the marker of CV risk, in the study group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activity is present in FDR of type2 diabetics. Increased resting heart rate, elevated hypertension status, decreased HRV and increased RPP in these subjects make them vulnerable to CV risks. SVI in these subjects contributes to CV risks independent of the degree of adiposity.

Statins and the autonomic nervous system

Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A 'pleiotropic' property of statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.

Hypertension Editors’ Picks

<i>Hypertension</i> Editors’ Picks

Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72-4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected.

Response to Glutamate Receptors and Presympathetic Neuronal Hyperactivity of the Central Nervous System in Hypertension

We thank Dr Tsuda1 for his interest in our work2 and his comments about the important role of N -methyl-d-aspartate (NMDA) receptors in the central nervous system in the control of sympathetic vasomotor tone in hypertension. In our recent publication, we reported that group II metabotropic glutamate receptors can be targeted to reduce sympathetic discharges by reducing synaptic glutamate release …

Disinhibition of RVLM neural circuits and regulation of sympathetic nerve discharge at peak hyperthermia

Hyperthermia is a potent activator of visceral sympathetic nerve discharge (SND), and the functional integrity of the rostral ventral lateral medulla (RVLM) is critically important for sustaining sympathoexcitation at peak hyperthermia. However, RVLM mechanisms mediating SND activation to acute heat stress are not well understood. Because RVLM GABA is tonically inhibitory to sympathetic nerve outflow, it is plausible to hypothesize that disinhibition of RVLM sympathetic neural circuits, via withdrawal of GABAergic tone, may affect SND regulation at peak hyperthermia. The effect of RVLM bicuculline (BIC; GABAA receptor antagonist, 100-200 pmol) microinjections on the level of renal SND in anesthetized rats was determined after internal body temperature (Tc) had been increased to 41.5°C. Temperature-control experiments involved RVLM BIC (100-200 pmol) microinjections, with Tc maintained at 38°C. As expected, acute heating significantly increased renal SND from control levels. Bilateral RVLM BIC microinjections at 41.5°C produced immediate and significant increases in renal SND above heating-induced levels of activation. Bilateral RVLM BIC microinjections at 38°C increased renal SND to similar levels as produced by RVLM BIC microinjections after Tc had been increased to 41.5°C (heating + RVLM BIC). These results demonstrate that a considerable level of RVLM GABAergic inhibition is sustained at peak hyperthermia, an interesting physiological response profile based on the significance of SND activation to cardiovascular regulation during heat stress.

Takotsubo cardiomyopathy after anti-influenza vaccination: catecholaminergic effects of immune system

Takotsubo cardiomyopathy (TTC) is a well-known condition, which leads to sudden transient regional systolic dysfunction. It mostly affects aging women and is usually precipitated by emotional or physical stress. Despite the tremendous amount of literature on TTC, cardiac sympathetic hyperactivity is the only thing known to be associated with pathogenesis. In our case, an elderly woman presented with an acute episode of TTC 24 hours after anti-influenza vaccination without any obvious stressor for sudden rise in the catecholamine level. Sudden postvaccination change in the cardiac sympathetic discharge is the most likely precipitant of TTC in this case.

Chlorthalidone: Mechanisms of Action and Effect on Cardiovascular Events

How chlorthalidone (CTDN) reduces risk for cardiovascular events (CVEs) can be considered in light of its ability to lower blood pressure (BP) and its non-BP related, pleiotropic effects. The mechanism by which CTDN lowers BP is unclear but may include alterations in whole body regulation and vasodilatory actions on vasculature, possibly mediated via its inhibitory effects on carbonic anhydrase. Additionally, CTDN has potentially beneficial, non-BP related, pleiotropic effects that include improvements in endothelial function, anti-platelet activity, and oxidative status. CTDN reduces pulse wave velocity, predictor of CVEs and a measure of central aortic stiffness associated with endothelial dysfunction. On the other hand, CTDN fosters hypokalemia, hyperglycemia, sympathetic discharge, and the renin-angiotensin-aldosterone system, but these potentially harmful effects do not appear to materially reduce CTDN's ability to prevent CVEs. Further, CTDN reduces and regresses left ventricular hypertrophy (LVH), an important BP-dependent predictor of CVEs. Consistent with this finding, CTDN was more effective than amlodipine in reducing congestive heart failure (CHF) in the Anti-hypertensive and Lipid-lowering Treatment to Prevent Heart Attach Trial (ALLHAT). In reducing CVEs, CTDN was superior to lisinopril in ALLHAT and superior to hydrochlorthiazide in observational cohort analyses and in network analyses of randomized trials. A statistical synthesis of randomized trials suggests that the reduction in cardiovascular risk from CTDN can be explained primarily on the basis of its ability to lower blood pressure rather than its influence upon non-BP related, pleiotropic effects.

Revelations about carotid body function through its pathological role in resistant hypertension.

Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension. We predict that carotid glomectomy will be a powerful way to temper excessive sympathetic discharge in diseases such as hypertension. We propose a model to explain that signalling from the ‘hypertensive’ carotid body is tonic, and hypothesise that there will be a sub-population of glomus cells that channel separately into reflex pathways controlling sympathetic motor outflows.

The Control of Male Sexual Responses

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

Physiological Changes Associated with de qi during electroacupuncture to LI4 and LI11: A randomised, placebo-controlled trial

Studies on the relationship between de qi intensity and activity changes in the autonomic nervous system (ANS) are scarce. This study investigates the physiological responses associated with de qi. The relationship between de qi intensity and such responses was determined. This was a single-blinded, randomised, placebo-controlled trial. A total of 36 subjects (19 men, 17 women), aged 34.5±4.6 years, were randomly assigned to group 1 (electroacupuncture at 2 Hz, 0.4 ms to right LI4 and LI11 for 30 min), group 2 (electroacupuncture stimulation to bilateral patellae) or group 3 (sham electroacupuncture to right LI4 and LI11 but over Duoderm pads). Heart rate (HR), mean arterial blood pressure (MAP) and HR variability by low/high frequency (LF/HF) were recorded 5 min before, during and 5 min after the intervention. Needle sensations were quantified by the Modified Massachusetts General Hospital Acupuncture Sensation Scale - Chinese version (C-MMASS) and the C-MMASS index was computed. A significant increase in LF/HF, MAP and HR was observed in group 1. A small and significant increase in LF/HF was observed in group 2 but the changes in MAP and HR in groups 2 and 3 were not significant. The C-MMASS index was highest in group 1 (5.3±1.3), moderate in group 2 (3.5±0.7) and lowest in group 3 (0.77±0.2). A positive correlation between de qi intensity and changes in LF/HF, MAP and HR was observed. This study suggests that de qi is associated with physiological changes, and that de qi intensity increases with an increase in sympathetic discharge of the ANS.

Lack of type VI adenylyl cyclase (AC6) leads to abnormal sympathetic tone in neonatal mice

Visceral functions are regulated by a basal sympathetic nerve discharge (SND), also known as ‘sympathetic tone’. We demonstrate herein that AC6 existed in tyrosine hydroxylase-positive rostral ventrolateral medulla neurons in the brainstem. Adenylyl cyclase (AC) assays showed lower basal and pituitary adenylate cyclase-activating peptide-evoked AC activities in the brainstem of AC6-null mice, indicating that AC6 is a prominent AC isozyme in the brainstem. Furthermore, two independent lines of AC6-null mice exhibited a much higher SND, recorded from splanchnic sympathetic nerves of neonatal brainstem–spinal cord preparations, than wildtype mice. An assay of urine noradrenaline confirmed this observation. Collectively, AC6 plays a critical role in the regulation of sympathetic tone.

Brown adipose tissue thermogenesis precedes food intake in genetically obese Zucker (fa/fa) rats

In Sprague–Dawley rats, brown adipose tissue (BAT) thermogenesis occurs in an episodic ultradian manner (BAT on-periods) as part of the basic rest–activity cycle (BRAC). Eating occurs approximately 15min after the onset of BAT on-periods. Zucker obese (fa/fa) rats eat larger less frequent meals than control rats. In chronically instrumented conscious unrestrained Zucker obese rats we examined ultradian fluctuations in BAT, body and brain temperatures, and the relation between BAT temperature and eating. The interval between BAT temperature peaks for the 12hour dark phase was 121±3 (mean±SE) min for Zucker obese rats and 91±3min for control lean rats (p<0.01). Corresponding values for the light phase were 148±6 and 118±4min (p<0.01). Mean BAT and body temperatures were lower in Zucker obese rats, in comparison with lean controls, during both BAT on-periods and BAT off-periods. Mean brain temperatures were lower during BAT off-periods. Amplitudes of the BRAC-related increases in all 3 temperatures were greater in the Zucker obese rats. Meal onset in Zucker obese rats commenced 15±1min after the onset of a BAT on-period, not significantly different for the delay observed in lean control rats (18±1min, p>0.05). Thus periods between eating are increased in the Zucker obese rats, but the action of leptin, absent in these animals, is not crucial for the timing of eating in relation to increases in BAT and body temperature. Lack of the normal excitatory action of leptin on brain-regulated BAT sympathetic discharge could also contribute to lower BAT thermogenesis in Zucker obese rats.

Glutamatergic activities in neonatal rat spinal cord heterogeneously regulate single-fiber splanchnic nerve discharge

Kynurenic acid (KYN) is a metabolite of tryptophan and is involved in various neurological disorders. Using whole-bundle nerve recording techniques, we previously observed that applications of KYN to block endogenous ionotropic glutamate receptor activities in neonatal rat spinal cords in vitro cause a reversible fluctuation of splanchnic sympathetic nerve discharge (SND). We hypothesized that the SND fluctuation was due to a heterogeneous single-fiber response. To detail individual fiber activities, we used the so-called 'oligofiber recordings'. Spontaneous single-fiber activities were recorded from the collagenase-dissociated splanchnic nerve fascicles. Applications of KYN increased, decreased or did not change firing rates. The heterogeneous responses in spontaneous spiking activities were confirmed by applications of APV or CNQX, suggesting an effect mediated by endogenous NMDA- or non-NMDA receptor activities. In addition to changes in firing rates, apparent drug-induced changes in firing patterns were also observed in some fiber activities. Using the oligofiber recording techniques, we confirmed a differential role of endogenous ionotropic glutamate receptor activities in regulating sympathetic outflows from the spinal cord of neonatal rats. Fine-tuning of ionotropic glutamate receptor activities in the spinal cord may serve as a simple way for heterogeneous regulation of various sympathetic-targeting tissues.