Role and mechanism of lncRNA under magnetic nanoparticles in atrial autonomic nerve remodeling during radiofrequency ablation of recurrent atrial fibrillation.

It aimed to investigate the mechanism of magnetic nanoparticles (MNPs) on atrial fibrillation and effect of n-isopropyl acrylamide coated MNPs (NIPA-co-MN) on the treatment of atrial fibrillation. Ten beagles weighing 20 - 25 kg were randomly divided into test group and control group. Dogs with atrial fibrillation were set as test group, and non-atrial fibrillation dogs as control group. The expression of long non-coding RNA (lncRNA) differentially expressed in the right anterior adipose pad in atrial fibrillation and non-atrial fibrillation dogs was detected by high-throughput sequencing. The relationship between lncRNA and cardiac autonomic nerve remodeling (CANR) was explored. In addition, 20 beagles weighing 20-25 kg were selected to study the therapeutic effect of n-isopropylacrylamide magnetic nanoparticles (NIPA-co-MN) on atrial fibrillation, and statistical analysis was performed. The volume and number of new neurons in the anterior right fat pad of atrium of test group were larger than the control group. The test group dogs produced 45 brand-new lncRNA, including 15 up-regulated transcripts and 30 down-regulated transcripts. MNPs injection can slow down the reduction of ventricular rate in right inferior ganglion plexus. The anterior right ganglion plexus resulted in a reduced amplitude of sinus tachyarrhythmia. This study provided references for the discovery of new diagnostic biomarkers or therapeutic targets and for the treatment of patients with atrial fibrillation.

Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction.

INTRODUCTION: Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. METHODS: Synthetic ghrelin was administered (100 µg·kg-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. RESULTS: MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (p < 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (p < 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (p < 0.01). DISCUSSION/CONCLUSION: Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.

The Effect of Castration on Peripheral Autonomic Neurons Supplying Mammalian Male Genitourinary System.

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed.

Nociceptive nerves regulate haematopoietic stem cell mobilization.

Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow-often referred to as 'niches'-that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves1,2. Although sympathetic nerves are known to regulate the HSC niche3-6, the contribution of nociceptive neurons in the bone marrow remains unclear. Here we show that nociceptive nerves are required for enforced HSC mobilization and that they collaborate with sympathetic nerves to maintain HSCs in the bone marrow. Nociceptor neurons drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via the secretion of calcitonin gene-related peptide (CGRP). Unlike sympathetic nerves, which regulate HSCs indirectly via the niche3,4,6, CGRP acts directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL) to promote egress by activating the Gαs/adenylyl cyclase/cAMP pathway. The ingestion of food containing capsaicin-a natural component of chili peppers that can trigger the activation of nociceptive neurons-significantly enhanced HSC mobilization in mice. Targeting the nociceptive nervous system could therefore represent a strategy to improve the yield of HSCs for stem cell-based therapeutic agents.

Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves.

Recent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D2 receptor knockout mice. I.c.v. injection of quinpirole and l-sulpiride each increased mRNA levels of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, which are the key enzymes for hepatic gluconeogenesis. Systemic injection of the ß2 adrenoceptor antagonist ICI 118,551 inhibited hyperglycemia induced by l-sulpiride, but not by quinpirole. In contrast, hyperglycemia induced by quinpirole, but not by l-sulpiride, was inhibited by hepatic vagotomy. These results suggest that stimulation of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves.

Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages.

Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. The risk of ASD is strongly associated with the prenatal period; for instance, the administration of valproic acid (VPA) to pregnant mothers increases risk of ASD in the child. Patients with ASD often exhibit an alteration in the autonomic nervous system. In this study, we assessed the autonomic nervous activity at each prenatal developmental stage of model mice of ASD treated with VPA, to clarify the relationship between timing of exposure and ASD symptoms. The assessment of the autonomic nervous activity was performed based on the analysis of electrocardiography data collected from fetal and adult mice. Interestingly, VPA model mouse fetuses exhibited a significantly lower activity of the sympathetic nervous system. In contrast, sympathetic nervous activity at P0 was significantly higher. In adult VPA model mice, the parasympathetic activity of female VPA mice was suppressed. Moreover, female VPA mice showed reduced the parasympathetic activity after exposure to restraint stress. These results suggest that the autonomic nervous activity of VPA model mice was altered from the fetal stage, and that the assessment of autonomic nervous activities at an early developmental stage could be useful for the understanding of ASD.

Targeting Ligands Deliver Model Drug Cargo into the Central Nervous System along Autonomic Neurons.

While biologic drugs such as proteins, peptides, or nucleic acids have shown promise in the treatment of neurodegenerative diseases, the blood-brain barrier (BBB) severely limits drug delivery to the central nervous system (CNS) after systemic administration. Consequently, drug delivery challenges preclude biological drug candidates from the clinical armamentarium. In order to target drug delivery and uptake into to the CNS, we used an in vivo phage display screen to identify peptides able to target drug-uptake by the vast array of neurons of the autonomic nervous system (ANS). Using next-generation sequencing, we identified 21 candidate targeted ANS-to-CNS uptake ligands (TACL) that enriched bacteriophage accumulation and delivered protein-cargo into the CNS after intraperitoneal (IP) administration. The series of TACL peptides were synthesized and tested for their ability to deliver a model enzyme (NeutrAvidin-horseradish peroxidase fusion) to the brain and spinal cord. Three TACL-peptides facilitated significant active enzyme delivery into the CNS, with limited accumulation in off-target organs. Peptide structure and serum stability is increased when internal cysteine residues are cyclized by perfluoroarylation with decafluorobiphenyl, which increased delivery to the CNS further. TACL-peptide was demonstrated to localize in parasympathetic ganglia neurons in addition to neuronal structures in the hindbrain and spinal cord. By targeting uptake into ANS neurons, we demonstrate the potential for TACL-peptides to bypass the blood-brain barrier and deliver a model drug into the brain and spinal cord.

Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus.

Microinjection of alamandine into the hypothalamic paraventricular nucleus (PVN) increased blood pressure and enhanced sympathetic activity. The aim of this study was to determine if superoxide anions modulate alamandine's effects in the PVN. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Microinjection of alamandine into the PVN increased MAP and RSNA in both WKY rats and SHRs, although to a greater extent in SHRs. These effects were blocked by pretreatment with an alamandine receptor (MrgD) antagonist D-Pro7-Ang-(1-7). Pretreatment with superoxide anion scavengers, tempol and tiron, and NADPH oxidase inhibitor apocynin (APO), also blocked the effects of alamandine on MAP and RSNA. In addition, pretreatment in the PVN with a superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the increases of MAP and RSNA induced by alamandine administration, with a greater response observed in SHRs. Superoxide anions and NADPH oxidase levels in the PVN were higher in SHRs than that in WKY rats. Alamandine treatment increased the levels of superoxide anions and NADPH oxidase in WKY and SHRs, however, with greater effect in SHRs. These alamandine-induced increases were inhibited by D-Pro7-Ang-(1-7) pretreatment in the PVN of both rats. These results demonstrate that superoxide anions in the PVN modulate alamandine-induced increases in blood pressure and sympathetic activity in both normotensive and hypertensive rats. Alamandine increases NADPH oxidase activity to induce superoxide anion production, which is mediated by the alamandine receptor.

The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies.

Small intestinal bacterial overgrowth (SIBO) is common among patients with HIV-associated autonomic neuropathies (HIV-AN) and may be associated with increased bacterial translocation and elevated plasma inflammatory biomarkers. Pyridostigmine is an acetylcholinesterase inhibitor which has been used to augment autonomic signaling. We sought preliminary evidence as to whether pyridostigmine could improve proximal gastrointestinal motility, reduce SIBO, reduce plasma sCD14 (a marker of macrophage activation and indirect measure of translocation), and reduce the inflammatory cytokines IL-6 and TNFα in patients with HIV-AN. Fifteen participants with well-controlled HIV, HIV-AN, and SIBO were treated with 8 weeks of pyridostigmine (30 mg PO TID). Glucose breath testing for SIBO, gastric emptying studies (GES) to assess motility, plasma sCD14, IL-6, and TNFα, and gastrointestinal autonomic symptoms were compared before and after treatment. Thirteen participants (87%) experienced an improvement in SIBO following pyridostigmine treatment; with an average improvement of 50% (p = 0.016). There was no change in gastrointestinal motility; however, only two participants met GES criteria for gastroparesis at baseline. TNFα and sCD14 levels declined by 12% (p = 0.004) and 19% (p = 0.015), respectively; there was no significant change in IL-6 or gastrointestinal symptoms. Pyridostigmine may ameliorate SIBO and reduce levels of sCD14 and TNFα in patients with HIV-AN. Larger placebo-controlled studies are needed to definitively delineate how HIV-AN affects gastrointestinal motility, SIBO, and systemic inflammation in HIV, and whether treatment improves clinical outcomes.

Effect of Lactobacillus delbrueckii LAB4 on hepatic and pancreatic sympathetic nerve activity and blood glucose levels in rats.

Various lactobacilli have been suggested to exert beneficial effects in humans. In this study, we examined the effects of intraduodenal (ID) administration of heat-killed Lactobacillus delbrueckii LAB4 (LAB4) on activities of efferent sympathetic nerves innervating the liver and pancreas. Consequently, it was observed that ID administration of LAB4 significantly reduced either the efferent hepatic sympathetic nerve activity (hepatic-SNA) or pancreatic sympathetic nerve activity (pancreatic-SNA) in urethane-anaesthetised rats. Moreover, the effect of acute and chronic administration of LAB4 (1×109 cells/ml) on hyperglycaemia induced by intracranial injection of 2-deoxy-D-glucose (2DG) were examined in conscious rats. We found that LAB4 significantly inhibited 2DG-induced hyperglycaemia. These findings suggest that ID administration of heat-killed LAB4 might lower plasma glucose level via changes in the autonomic nervous system in rats.

Insulin-responsive autonomic neurons in rat medulla oblongata.

Low blood glucose activates brainstem adrenergic and cholinergic neurons, driving adrenaline secretion from the adrenal medulla and glucagon release from the pancreas. Despite their roles in maintaining glucose homeostasis, the distributions of insulin-responsive adrenergic and cholinergic neurons in the medulla are unknown. We fasted rats overnight and gave them insulin (10 U/kg i.p.) or saline after 2 weeks of handling. Blood samples were collected before injection and before perfusion at 90 min. We immunoperoxidase-stained transverse sections of perfused medulla to show Fos plus either phenylethanolamine N-methyltransferase (PNMT) or choline acetyltransferase (ChAT). Insulin injection lowered blood glucose from 4.9 ± 0.3 mmol/L to 1.7 ± 0.2 mmol/L (mean ± SEM; n = 6); saline injection had no effect. In insulin-treated rats, many PNMT-immunoreactive C1 neurons had Fos-immunoreactive nuclei, with the proportion of activated neurons being highest in the caudal part of the C1 column. In the rostral ventrolateral medulla, 33.3% ± 1.4% (n = 8) of C1 neurons were Fos-positive. Insulin also induced Fos in 47.2% ± 2.0% (n = 5) of dorsal medullary C3 neurons and in some C2 neurons. In the dorsal motor nucleus of the vagus (DMV), insulin evoked Fos in many ChAT-positive neurons. Activated neurons were concentrated in the medial and middle regions of the DMV beneath and just rostral to the area postrema. In control rats, very few C1, C2, or C3 neurons and no DMV neurons were Fos-positive. The high numbers of PNMT-immunoreactive and ChAT-immunoreactive neurons that express Fos after insulin treatment reinforce the importance of these neurons in the central response to a decrease in glucose bioavailability.

Hippocampal modulation of cardiorespiratory function.

Changes in cardiorespiratory control accompany the expression of complex emotions, indicative of limbic brain inputs onto bulbar autonomic pathways. Previous studies have focussed on the role of the prefrontal cortex in autonomic regulation. However, the role of the hippocampus, also important in limbic processing, has not been addressed in detail. Anaesthetised, instrumented rats were used to map the location of hippocampal sites capable of evoking changes in cardiorespiratory control showing that stimulation of discrete regions within the CA1 fields of both the dorsal and ventral hippocampus potently alter breathing and cardiovascular activity. Additionally, tracing of the neuroanatomical tracts and pharmacological inactivation studies were used to demonstrate a role of the basomedial amygdala in hippocampal evoked responses. Collectively, these data support the existence of a hippocampal-amygdala neural circuit capable of modulating bulbar cardiorespiratory control networks and may suggest a role for this circuit in the top-down regulation of breathing and autonomic outflow necessary for the expression of complex emotions.

Changes in sympathetic neurovascular function following spinal cord injury.

The effects of spinal cord injury (SCI) on sympathetic neurovascular transmission have generally been ignored. This review describes changes in sympathetic nerve-mediated activation of arterial vessels to which ongoing sympathetic activity has been reduced or silenced following spinal cord transection in rats. In all vessels studied in rats, SCI markedly enhanced their contractile responses to nerve activity. However, the mechanisms that augment neurovascular transmission differ between the rat tail artery and mesenteric artery. In tail artery, the enhancement of neurovascular transmission cannot be attributed to changes in sensitivity of the vascular muscle to α1- or α2-adrenoceptor agonists. Instead the contribution of L-type Ca2+ channels to activation of the smooth muscle by nerve-released noradrenaline is greatly increased following SCI. By contrast, mesenteric arteries from SCI rats had increased sensitivity to phenylephrine but not to methoxamine. While both phenylephrine and methoxamine are α1-adrenoceptor agonists, only phenylephrine is a substrate for the neuronal noradrenaline transporter. Therefore the selective increase in sensitivity to phenylephrine suggests that the activity of the neuronal noradrenaline transporter is reduced. While present evidence suggests that sympathetic vasoconstrictor neurons do not contribute to the normal regulation of peripheral resistance below a complete SCI in humans, the available evidence does indicate that these experimental findings in animals are likely to apply after SCI in humans and contribute to autonomic dysreflexia.

Baroreflex autonomic control in human spinal cord injury: Physiology, measurement, and potential alterations.

The arterial baroreflex is a primary regulator of autonomic outflow to effectively regulate acute changes in blood pressure. After a spinal cord injury (SCI), regulation of autonomic function is disrupted, although the damage of the autonomic pathways may not necessarily be related to the severity of injury (i.e. level and completeness). Nonetheless, it can be assumed that there would be greater loss of sympathetic innervation with higher level of injury and that cardiac parasympathetic control would remain intact regardless of injury level. In those with SCI, impaired baroreflex regulation has implications not only for adequate pressure regulation, but also for long term cardiovascular health. In this review, we discuss the expected impact ofan SCI on baroreflex control and the studies that have investigated baroreflex sensitivity in this population. The data generally indicates that baroreflex sensitivity is lesser in those with chronic injuries. However, these findings are counter to the expected effect of an SCI and hence may indicate that the effect of an SCI on baroreflex control might be secondary to long term deconditioning and/or vascular stiffening of baroreceptive arteries. Furthermore, the alterations in the ability to regulate pressure do not impact the relationship between spontaneous heart rate and blood pressure variabilities. In addition, those with SCI are not adequately able to control blood pressure changes in response to orthostasis, resulting in frank hypotension in a significant proportion of those with high level injuries.

Electrophysiological study on sensory nerve activity from the submandibular salivary gland in rats.

To evaluate the role of afferent information from the salivary gland, we analyzed the neural activity of the sensory nerve innervating the submandibular gland in anesthetized rats. The sensory nerves running through the parasympathetic nerve supply responded to mechanical pressure applied to the surface of the main duct and the body of the gland, whilst those in the sympathetic nerve supply responded only to the body of the gland. The sensory nerves in the sympathetic and parasympathetic nerve routes responded to pressure in the duct system produced by a retrograde injection of saline into the main duct. The threshold pressure for production of afferent discharges was higher than the maximum secretory pressure evoked by electrical stimulation of the parasympathetic secretory nerve. The retrograde ductal injection of drugs related to the inflammatory process (capsaicin and bradykinin) evoked intense multi-unit discharges in the sensory nerves of both routes. The sensory nerve in the sympathetic route was responsive to ligation of the artery to the gland. These results suggest that sensory nerves in the sympathetic and parasympathetic routes mainly conduct noxious information, and that those in the sympathetic route are responsive to ischemia and may control blood flow of the gland.

Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients.

OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities. METHODS: We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences. RESULTS: Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001). CONCLUSIONS: Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.

Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study.

BACKGROUND: The role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs). METHODS: We incorporated the morphology of the GP and parasympathetic nerves in a three-dimensional (3D) realistic LA model. For the model of ionic currents, we used a human atrial model. GPs were stimulated by increasing the IK[ACh], and sympathetic nerve stimulation was conducted through a homogeneous increase in the ICa-L. ANS-induced wave-dynamics changes were evaluated in a model that integrated a patient's LA geometry, and we repeated simulation studies using LA geometries from 10 different patients. RESULTS: The two-dimensional model of pulmonary vein (PV) cells exhibited late phase 3 early afterdepolarization-like activity under 0.05µM acetylcholine (ACh) stimulation. In the 3D simulation model, PV tachycardia was induced, which degenerated to AF via GP (0.05µM ACh) and sympathetic (7.0×ICa-L) stimulations. Under sustained AF, local reentries were observed at the LA-PV junction. We also observed that GP stimulation reduced the complex fractionated atrial electrogram (CFAE)-cycle length (CL, p<0.01) and the life span of phase singularities (p<0.01). GP stimulation also increased the overlap area of the GP and CFAE areas (CFAE-CL≤120ms, p<0.01). When 3 patterns of virtual ablations were applied to the 3D AF models, circumferential PV isolation including the GP was the most effective in terminating AF. CONCLUSION: Cardiac ANS stimulations demonstrated triggered activity, automaticity, and local reentries at the LA-PV junction, as well as co-localized GP and CFAE areas in the 3D in silico GP model of the LA.

Perifornical hypothalamic pathway to the adrenal gland: Role for glutamatergic transmission in the glucose counter-regulatory response.

Adrenaline is an important counter-regulatory hormone that helps restore glucose homeostasis during hypoglycaemia. However, the neurocircuitry that connects the brain glucose sensors and the adrenal sympathetic outflow to the chromaffin cells is poorly understood. We used electrical microstimulation of the perifornical hypothalamus (PeH) and the rostral ventrolateral medulla (RVLM) combined with adrenal sympathetic nerve activity (ASNA) recording to examine the relationship between the RVLM, the PeH and ASNA. In urethane-anaesthetised male Sprague-Dawley rats, intermittent single pulse electrical stimulation of the rostroventrolateral medulla (RVLM) elicited an evoked ASNA response that consisted of early (60±3ms) and late peaks (135±4ms) of preganglionic and postganglionic activity. In contrast, RVLM stimulation evoked responses in lumbar sympathetic nerve activity that were almost entirely postganglionic. PeH stimulation also produced an evoked excitatory response consisting of both preganglionic and postganglionic excitatory peaks in ASNA. Both peaks in ASNA following RVLM stimulation were reduced by intrathecal kynurenic acid (KYN) injection. In addition, the ASNA response to systemic neuroglucoprivation induced by 2-deoxy-d-glucose was abolished by bilateral microinjection of KYN into the RVLM. This suggests that a glutamatergic pathway from the perifornical hypothalamus (PeH) relays in the RVLM to activate the adrenal SPN and so modulate ASNA. The main findings of this study are that (i) adrenal premotor neurons in the RVLM may be, at least in part, glutamatergic and (ii) that the input to these neurons that is activated during neuroglucoprivation is also glutamatergic.

Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity.

BACKGROUND: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. METHODS: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. RESULTS: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms 2 , P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. CONCLUSIONS: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.