Myocardial Infarction Causes Transient Cholinergic Transdifferentiation of Cardiac Sympathetic Nerves via gp130.

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Olivas, Antoinette; Gardner, Ryan T; Wang, Lianguo; Ripplinger, Crystal M; Woodward, William R; Habecker, Beth A

2016-01-13

Sympathetic and parasympathetic control of the heart is a classic example of norepinephrine (NE) and acetylcholine (ACh) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of β receptors, whereas parasympathetic ACh slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to ACh and we provide evidence that mouse cardiac sympathetic nerves transiently produce ACh after myocardial infarction (MI). ACh levels increased in viable heart tissue 10-14 d after MI, returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for ACh synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after MI revealed choline acetyltransferase (ChAT) in stellate sympathetic neurons and vesicular ACh transporter immunoreactivity in tyrosine hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the ChAT gene from adult sympathetic neurons prevented the infarction-induced increase in cardiac ACh. Deletion of the gp130 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons. Ex vivo experiments examining the effect of NE and ACh on rabbit cardiac action potential duration revealed that ACh blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. This raises the possibility that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility. Sympathetic neurons normally make norepinephrine (NE), which increases heart rate and the contractility of cardiac myocytes. We found that, after myocardial infarction, the sympathetic neurons

Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

DEFF Research Database (Denmark)

Pedersen, J L; Rung, G W; Kehlet, H

1997-01-01

BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....... The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds...... between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. CONCLUSION: Sympathetic nerve block did not change...

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

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Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

2010-04-01

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (Pdiet rabbits and was correlated to plasma leptin (r=0.87; Pfat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images.

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Brown, Rachael; James, Cheree; Henderson, Luke A; Macefield, Vaughan G

2012-01-01

The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

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Limberg, Jacqueline K; Malterer, Katherine R; Matzek, Luke J; Levine, James A; Charkoudian, Nisha; Miles, John M; Joyner, Michael J; Curry, Timothy B

2017-08-01

Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following β -adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic β -adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and β -blockade (AUC P ropranolol -AUC S aline , β -REE) and as a percent (%) of control (AUC P ropranolol ÷AUC S aline  × 100). β -REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: β -REE R  =   -0.58, P =  0.03; %REE R  = -0.56, P =  0.04; NE: β -REE R  = -0.55, P  = 0.0535; %REE R  = -0.54, P  = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Intracranial Pressure Is a Determinant of Sympathetic Activity

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Eric A. Schmidt

2018-02-01

Full Text Available Intracranial pressure (ICP is the pressure within the cranium. ICP rise compresses brain vessels and reduces cerebral blood delivery. Massive ICP rise leads to cerebral ischemia, but it is also known to produce hypertension, bradycardia and respiratory irregularities due to a sympatho-adrenal mechanism termed Cushing response. One still unresolved question is whether the Cushing response is a non-synaptic acute brainstem ischemic mechanism or part of a larger physiological reflex for arterial blood pressure control and homeostasis regulation. We hypothesize that changes in ICP modulates sympathetic activity. Thus, modest ICP increase and decrease were achieved in mice and patients with respectively intra-ventricular and lumbar fluid infusion. Sympathetic activity was gauged directly by microneurography, recording renal sympathetic nerve activity in mice and muscle sympathetic nerve activity in patients, and gauged indirectly in both species by heart-rate variability analysis. In mice (n = 15, renal sympathetic activity increased from 29.9 ± 4.0 bursts.s−1 (baseline ICP 6.6 ± 0.7 mmHg to 45.7 ± 6.4 bursts.s−1 (plateau ICP 38.6 ± 1.0 mmHg and decreased to 34.8 ± 5.6 bursts.s−1 (post-infusion ICP 9.1 ± 0.8 mmHg. In patients (n = 10, muscle sympathetic activity increased from 51.2 ± 2.5 bursts.min−1 (baseline ICP 8.3 ± 1.0 mmHg to 66.7 ± 2.9 bursts.min−1 (plateau ICP 25 ± 0.3 mmHg and decreased to 58.8 ± 2.6 bursts.min−1 (post-infusion ICP 14.8 ± 0.9 mmHg. In patients 7 mmHg ICP rise significantly increases sympathetic activity by 17%. Heart-rate variability analysis demonstrated a significant vagal withdrawal during the ICP rise, in accordance with the microneurography findings. Mice and human results are alike. We demonstrate in animal and human that ICP is a reversible determinant of efferent sympathetic outflow, even at relatively low ICP levels. ICP is a biophysical stress related to the forces within the brain. But ICP

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

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Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

International Nuclear Information System (INIS)

Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A. Neto

2014-01-01

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Energy Technology Data Exchange (ETDEWEB)

Tiradentes, R.V. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Pires, J.G.P. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Silva, N.F. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Ramage, A.G. [Department of Neuroscience, Physiology and Pharmacology, University College London, London (United Kingdom); Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Futuro, H.A. Neto [Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

2014-05-30

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

The pedunculopontine tegmentum controls renal sympathetic nerve activity and cardiorespiratory activities in nembutal-anesthetized rats.

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Anne M Fink

Full Text Available Elevated renal sympathetic nerve activity (RSNA accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response. Peak increases in RSNA occurred within 10-20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites, suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to

Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

International Nuclear Information System (INIS)

Meguro, Kentaro; Nagai, Ryozo; Toyama, Takuji; Adachi, Hitoshi; Ohshima, Shigeru; Taniguchi, Koichi

2007-01-01

Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF) 5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO 2 and 93% O 2 ). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is

Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.

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Yamanouchi, Kosho; Hayashida, Naomi; Kuba, Sayaka; Sakimura, Chika; Kuroki, Tamotsu; Togo, Michita; Katayama, Noritada; Takamura, Noboru; Eguchi, Susumu

2015-11-01

Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

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Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

2011-11-01

Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

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Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

Electroacupuncture Improved the Function of Myocardial Ischemia Involved in the Hippocampus-Paraventricular Nucleus-Sympathetic Nerve Pathway

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Shuai Cui

2018-01-01

Full Text Available We investigated the hippocampus-paraventricular nucleus- (PVN- sympathetic nerve pathway in electroacupuncture (EA at the heart meridian for the treatment of myocardial ischemia by observing PVN neuronal discharge, sympathetic nerve discharge, and hemodynamics parameters. Sprague Dawley (SD rats were equally divided into four groups: Sham, Model, Model + EA, and Model + EA + Lesion. The model rat was established by ligating the left anterior descending branch of the coronary artery. Changes in the sympathetic nerve discharge and hemodynamic parameters were observed. The Model + EA exhibited a significantly lower discharge frequency of PVN neurons compared with the Model. The Model + EA + Lesion had a significantly higher discharge frequency compared with the Model + EA. The total discharge frequency of PVN neurons and interneurons were positively correlated with the sympathetic nerve discharge. The total discharge frequency of PVN neurons was positively correlated with heart rate (HR and negatively correlated with mean arterial pressure (MAP and rate pressure product (RPP. The discharge frequency of interneurons was positively correlated with HR and negatively correlated with MAP and RPP. The hippocampus-PVN-sympathetic nerve pathway is involved in electroacupuncture at the heart meridian and interneurons are the key neurons in PVNs.

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans.

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Kaufmann, H; Biaggioni, I; Voustianiouk, A; Diedrich, A; Costa, F; Clarke, R; Gizzi, M; Raphan, T; Cohen, B

2002-04-01

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

Change in sympathetic nerve firing pattern associated with dietary weight loss in the metabolic syndrome

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Elisabeth Annie Lambert

2011-08-01

Full Text Available Sympathetic activation in subjects with the metabolic syndrome (MS plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the firing behavior of single-unit sympathetic nerve fibres. Fourteen subjects (57±2 years, 9 men, 5 females fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters and multi-unit and single unit muscle sympathetic nerve activity (MSNA, microneurography were assessed prior to and at the end of the diet. Patients’ weight dropped from 96±4 to 88±3 kg (P<0.001. This was associated with a decrease in systolic and diastolic blood pressure (-12 ±3 and -5±2 mmHg, P<0.05, and in heart rate (-7±2 bpm, P<0.01 and an improvement in all metabolic parameters (fasting glucose: -0.302.1±0.118 mmol/l, total cholesterol: -0.564±0.164 mmol/l, triglycerides: -0.414±0.137 mmol/l, P<0.05. Multi-unit MSNA decreased from 68±4 to 59±5 bursts per 100 heartbeats (P<0.05. Single-unit MSNA indicated that the firing rate of individual vasoconstrictor fibres decreased from 59±10 to 32±4 spikes per 100 heart beats (P<0.05. The probability of firing decreased from 34±5 to 23±3 % of heartbeats (P<0.05, and the incidence of multiple firing decreased from 14±4 to 6±1 % of heartbeats (P<0.05. Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57±0.69 to 9.57±1.20 msec.mmHg-1; sympathetic slope: -3.86±0.34 to -5.05±0.47 bursts per 100 heartbeats.mmHg-1 P<0.05 for both. Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the firing pattern of

Role of renal sympathetic nerve activity in prenatal programming of hypertension.

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Baum, Michel

2018-03-01

Prenatal insults, such as maternal dietary protein deprivation and uteroplacental insufficiency, lead to small for gestational age (SGA) neonates. Epidemiological studies from many different parts of the world have shown that SGA neonates are at increased risk for hypertension and early death from cardiovascular disease as adults. Animal models, including prenatal administration of dexamethasone, uterine artery ligation and maternal dietary protein restriction, result in SGA neonates with fewer nephrons than controls. These models are discussed in this educational review, which provides evidence that prenatal insults lead to altered sodium transport in multiple nephron segments. The factors that could result in increased sodium transport are discussed, focusing on new information that there is increased renal sympathetic nerve activity that may be responsible for augmented renal tubular sodium transport. Renal denervation abrogates the hypertension in programmed rats but has no effect on control rats. Other potential factors that could cause hypertension in programmed rats, such as the renin-angiotensin system, are also discussed.

Does transcutaneous nerve stimulation have effect on sympathetic skin response?

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Okuyucu, E Esra; Turhanoğlu, Ayşe Dicle; Guntel, Murat; Yılmazer, Serkan; Savaş, Nazan; Mansuroğlu, Ayhan

2018-01-01

This study examined the effects of transcutaneous electrical nerve stimulation (TENS) on the sympathetic nerve system by sympathetic skin response test. Fifty-five healthy volunteers received either: (i) 30minutes TENS (25 participants) (ii) 30minutes sham TENS (30 participants) and SSR test was performed pre- and post-TENS. The mean values of latency and peak-to-peak amplitude of five consecutive SSRs were calculated. A significant amplitude difference was found between TENS and sham TENS group both in right and left hand (p=0.04, p=0.01, respectively). However there was no significant latancy difference between two groups (p>0.05 ). TENS has an inhibitory effect on elicited SNS responses when compared with sham TENS control group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

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Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

2014-01-01

Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia.

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Jouett, Noah P; Moralez, Gilbert; Raven, Peter B; Smith, Michael L

2017-04-01

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in 1 ) SNA discharge and 2 ) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. NEW & NOTEWORTHY This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients. Copyright © 2017 the American Physiological Society.

Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

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Ibrahim M Salman

2015-08-01

Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

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Scott S Wildman

2013-10-01

Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

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Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

2018-01-27

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG

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Kiyono, Yasushi; Kajiyama, Satomi; Fujiwara, Hiromi; Kanegawa, Naoki; Saji, Hideo

2005-01-01

Cardiac scintigraphic studies using 123 I-labeled metaiodobenzylguanidine ([ 123 I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways. Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [ 125 I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay. The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats. The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall. (orig.)

Sympathetic activation during early pregnancy in humans

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Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

2012-01-01

Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

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Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

2000-07-01

This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

Effect of percutaneous renal sympathetic nerve radiofrequency ablation in patients with severe heart failure.

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Dai, Qiming; Lu, Jing; Wang, Benwen; Ma, Genshan

2015-01-01

This study aimed to investigate the clinical feasibility and effects of percutaneous renal sympathetic nerve radiofrequency ablation in patients with heart failure. A total of 20 patients with heart failure were enrolled, aged from 47 to 75 years (63±10 years). They were divided into the standard therapy (n = 10), and renal nerve radiofrequency ablation groups (n = 10). There were 15 males and 5 female patients, including 8 ischemic cardiomyopathy, 8 dilated cardiomyopathy, and 8 hypertensive cardiopathy. All of the patients met the criteria of New York Heart Association classes III-IV cardiac function. Patients with diabetes and renal failure were excluded. Percutaneous renal sympathetic nerve radiofrequency ablation was performed on the renal artery wall under X-ray guidance. Serum electrolytes, neurohormones, and 24 h urine volume were recorded 24 h before and after the operation. Echocardiograms were performed to obtain left ventricular ejection fraction at baseline and 6 months. Heart rate, blood pressure, symptoms of dyspnea and edema were also monitored. After renal nerve ablation, 24 h urine volume was increased, while neurohormone levels were decreased compared with those of pre-operation and standard therapy. No obvious change in heart rate or blood pressure was recorded. Symptoms of heart failure were improved in patients after the operation. No complications were recorded in the study. Percutaneous renal sympathetic nerve radiofrequency ablation may be a feasible, safe, and effective treatment for the patients with severe congestive heart failure.

Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure. Comparison with enalapril

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Tsutamoto, Takayoshi; Tanaka, Toshinari; Sakai, Hiroshi

2008-01-01

In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP. (author)

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

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Baron, R; Wasner, G; Borgstedt, R; Hastedt, E; Schulte, H; Binder, A; Kopper, F; Rowbotham, M; Levine, J D; Fields, H L

1999-03-23

Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats.

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Jie Song

Full Text Available During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF and lumbar sympathetic nerve activity (LSNA mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group: (1 non-sensitized, (2 anaphylaxis, (3 anaphylaxis-lumbar sympathectomy (LS and (4 anaphylaxis-sinoaortic denervation (SAD groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP, heart rate (HR, central venous pressure (CVP, FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats.

Comparison of sympathetic nerve responses to neck and forearm isometric exercise

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Steele, S. L. Jr; Ray, C. A.

2000-01-01

PURPOSE: Although the autonomic and cardiovascular responses to arm and leg exercise have been studied, the sympathetic adjustments to exercise of the neck have not. The purpose of the present study was twofold: 1) to determine sympathetic and cardiovascular responses to isometric contractions of the neck extensors and 2) to compare sympathetic and cardiovascular responses to isometric exercise of the neck and forearm. METHODS: Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate were measured in nine healthy subjects while performing isometric neck extension (INE) and isometric handgrip (IHG) in the prone position. After a 3-min baseline period, subjects performed three intensities of INE for 2.5 min each: 1) unloaded (supporting head alone), 2) 10% maximal voluntary contraction (MVC), and 3) 30% MVC, then subjects performed two intensities (10% and 30% MVC) of IHG for 2.5 min. RESULTS: Supporting the head by itself did not significantly change any of the variables. During [NE, MAP significantly increased by 10 +/- 2 and 31 +/- 4 mm Hg and MSNA increased by 67 +/- 46 and 168 +/- 36 units/30 s for 10% and 30% MVC, respectively. IHG and INE evoked similar responses at 10% MVC, but IHG elicited higher peak MAP and MSNA at 30% MVC (37 +/- 7 mm Hg (P INE can elicit marked increases in MSNA and cardiovascular responses but that it evokes lower peak responses as compared to IHG. We speculate that possible differences in muscle fiber type composition, muscle mass, and/or muscle architecture of the neck and forearm are responsible for these differences in peak responses.

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

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Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

2006-04-01

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

Effect of 4G-alpha-glucopyranosyl hesperidin on brown fat adipose tissue- and cutaneous-sympathetic nerve activity and peripheral body temperature.

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Shen, Jiao; Nakamura, Hiroyasu; Fujisaki, Yoshiyuki; Tanida, Mamoru; Horii, Yuko; Fuyuki, Risa; Takumi, Hiroko; Shiraishi, Koso; Kometani, Takashi; Nagai, Katsuya

2009-09-11

Changes in the activity of the autonomic nervous system are good indicators of alterations in physiological phenomena such as the body temperature, blood glucose, blood pressure. Hesperidin, a flavanone known as vitamin P, has been shown to reduce the levels of serum lipids, cholesterol, and blood pressure. However, hesperidin is not water-soluble and is not well absorbed from the intestine. G-hesperidin (4G-alpha-glucopyranosyl hesperidin) is more water-soluble and more rapidly absorbed than hesperidin. In order to clarify the functions of G-hesperidin, we examined the effects of oral administration of G-hesperidin on interscapular brown adipose tissue-sympathetic nerve activity (BAT-SNA) and cutaneous sympathetic nerve activity (CASNA) in rats weighing about 300 g. In this study, we found that oral administration of 60 mg of G-hesperidin increased the BAT-SNA but decreased the CASNA in urethane-anesthetized rats. Since an elevation in BAT-SNA increases heat production (i.e. body temperature (BT)) and a decrease in CASNA increases cutaneous perfusion, we examined whether oral administration of G-hesperidin had an effect on the peripheral BT in rats. Consequently, we observed that the subcutaneous BT at the caudal end of the back after oral administration of 60 mg of G-hesperidin was significantly higher than the subcutaneous BT after oral administration of water in conscious rats. These findings suggest that G-hesperidin enhances the BAT-SNA and suppresses the CASNA resulting in an increase in the peripheral BT, probably by an increase in the thermogenesis in the BAT and an elevation in the cutaneous blood flow.

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

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Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

2016-01-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

Pet measurements of presynaptic sympathetic nerve terminals in the heart

International Nuclear Information System (INIS)

Schwaiger, M.; Hutchins, G.D.; Wieland, D.M.

1991-01-01

[ 18 F]Metaraminol (FMR) and [ 11 C]hydroxyephedrine (HED) are catecholamine analogues that have been developed at the University of Michigan for the noninvasive characterization of the sympathetic nervous system of the heart using positron emission tomography (PET). Pharmacological studies employing neurotoxins and uptake inhibitors have demonstrated that both FMR and HED specifically trace the uptake and storage of catecholamines in sympathetic nerve terminals with little nonspecific tracer accumulation. These compounds exhibit excellent qualitative imaging characteristics with heart-to-blood ratios exceeding 6:1 as early as 15 min after intravenous injection in both animals (HED and FMR) and humans (HED). Tracer kinetic modeling techniques have been employed for the quantitative assessment of neuronal catecholamine uptake and storage. Indices of neuronal function, such as the volume of tracer distribution derived from the kinetic models, have been employed in preliminary human studies. Comparison of the tissue distribution volume of HED between normal (control subjects) and denervated (recent transplant patients) cardiac tissue demonstrates a dynamic range of approximately 5:1. This distribution volume is reduced by 60% from normal in patients with dilated cardiomyopathy, indicating dysfunction of the sympathetic system. These results show that HED used in combination with PET provides a sophisticated quantitative approach for studying the sympathetic nervous system of the normal and diseased human heart

Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

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Daniel eBoulton

2016-05-01

Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

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Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

2016-08-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. Copyright © 2016 the American Physiological Society.

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

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Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

2013-09-01

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy. A comparison of 123I-MIBG scintigraphic and echocardiographic data

International Nuclear Information System (INIS)

Naruse, Hitoshi; Arii, Tohru; Kondo, Tomohiro

2000-01-01

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123 I-MIBG scintigraphy. Both of these methods are associated with β-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patents with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography; and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123[ 123 I]meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123 I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r=0.682, p=0.0146), wall motion after dobutamine stress (r=0.758, p=0.0043), the change in wall motion (r=0.667, p=0.0178), and with left ventricular diastolic diameter (r=0.837, p=0.0007). In addition, the 123 I-MIBG washout rate correlated with baseline wall motion (r=0.608, p=0.0360), wall motion after dobutamine stress (r=0.703, p=0.0107), and with the change in wall motion (r=0.664, p=0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure. (author)

Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.

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Somers, V K; Mark, A L; Zavala, D C; Abboud, F M

1989-11-01

The sympathetic response to hypoxia depends on the interaction between chemoreceptor stimulation (CRS) and the associated hyperventilation. We studied this interaction by measuring sympathetic nerve activity (SNA) to muscle in 13 normal subjects, while breathing room air, 14% O2, 10% O2, and 10% O2 with added CO2 to maintain isocapnia. Minute ventilation (VE) and blood pressure (BP) increased significantly more during isocapnic hypoxia (IHO) than hypocapnic hypoxia (HHO). In contrast, SNA increased more during HHO [40 +/- 10% (SE)] than during IHO (25 +/- 19%, P less than 0.05). To determine the reason for the lesser increase in SNA with IHO, 11 subjects underwent voluntary apnea during HHO and IHO. Apnea potentiated the SNA responses to IHO more than to HHO. SNA responses to IHO were 17 +/- 7% during breathing and 173 +/- 47% during apnea whereas SNA responses to HHO were 35 +/- 8% during breathing and 126 +/- 28% during apnea. During ventilation, the sympathoexcitation of IHO (compared with HHO) is suppressed, possibly for two reasons: 1) because of the inhibitory influence of activation of pulmonary afferents as a result of a greater increase in VE, and 2) because of the inhibitory influence of baroreceptor activation due to a greater rise in BP. Thus in humans, the ventilatory response to chemoreceptor stimulation predominates and restrains the sympathetic response. The SNA response to chemoreceptor stimulation represents the net effect of the excitatory influence of the chemoreflex and the inhibitory influence of pulmonary afferents and baroreceptor afferents.

The sympathetic innervation of the heart: Important new insights.

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Coote, J H; Chauhan, R A

2016-08-01

Autonomic control of the heart has a significant influence over development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic activity is known to be upregulated during these conditions and hence the sympathetic nerves present a target for treatment. However, a better understanding of the anatomy and physiology of cardiac sympathetic nerves is required for the progression of clinical interventions. This review explores the organization of the cardiac sympathetic nerves, from the preganglionic origin to the postganglionic innervations, and provides an overview of literature surrounding anti-arrhythmic therapies including thoracic sympathectomy and dorsal spinal cord stimulation. Several features of the innervation are clear. The cardiac nerves differentially supply the nodal and myocardial tissue of the heart and are dependent on activity generated in spinal neurones in the upper thoracic cord which project to synapse with ganglion cells in the stellate complex on each side. Networks of spinal interneurones determine the pattern of activity. Groups of spinal neurones selectively target specific regions of the heart but whether they exhibit a functional selectivity has still to be elucidated. Electrical or ischemic signals can lead to remodeling of nerves in the heart or ganglia. Surgical and electrical methods are proving to be clinically beneficial in reducing atrial and ventricular arrhythmias, heart failure and severe cardiac pain. This is a rapidly developing area and we need more basic understanding of how these methods work to ensure safety and reduction of side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

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Arnold, Julia; Barcena de Arellano, Maria L; Rüster, Carola; Vercellino, Giuseppe F; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

2012-01-01

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain. Copyright © 2011 Elsevier Inc. All rights reserved.

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder.

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Park, Jeanie; Marvar, Paul J; Liao, Peizhou; Kankam, Melanie L; Norrholm, Seth D; Downey, Ryan M; McCullough, S Ashley; Le, Ngoc-Anh; Rothbaum, Barbara O

2017-07-15

Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients. Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress:  combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

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Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

2018-06-29

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by {sup 11}C-hydroxyephedrine

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Werner, Rudolf A.; Higuchi, Takahiro [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Maya, Yoshifumi [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nihon Medi-Physics Co., Ltd., Research Centre, Chiba (Japan); Rischpler, Christoph [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Muenchen (Germany); Javadi, Mehrbod S. [Johns Hopkins University, Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Fukushima, Kazuhito [Hyogo College of Medicine, Department of Radiology, Hyogo (Japan); Lapa, Constantin [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, Ken [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

2016-02-15

An altered state of the cardiac sympathetic nerves is an important prognostic factor in patients with coronary artery disease. The aim of this study was to investigate regional sympathetic nerve damage and restoration utilizing a rat model of myocardial transient ischemia and a catecholamine analog PET tracer, {sup 11}C-hydroxyephedrine ({sup 11}C-HED). Transient myocardial ischemia was induced by coronary occlusion for 20 min and reperfusion in male Wistar rats. Dual-tracer autoradiography was performed subacutely (7 days) and chronically (2 months) after ischemia, and in control rats without ischemia using {sup 11}C-HED as a marker of sympathetic innervation and {sup 201}TI for perfusion. Additional serial in vivo cardiac {sup 11}C-HED and {sup 18}F-FDG PET scans were performed in the subacute and chronic phases after ischemia. After transient ischemia, the {sup 11}C-HED uptake defect areas in both the subacute and chronic phases were clearly larger than the perfusion defect areas in the midventricular wall. The subacute {sup 11}C-HED uptake defect showed a transmural pattern, whereas uptake recovered in the subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve staining confirmed regional denervation corresponding to areas of decreased {sup 11}C-HED uptake. Serial in vivo PET imaging visualized reductions in the area of the {sup 11}C-HED uptake defects in the chronic phase consistent with autoradiography and histology. Higher susceptibility of sympathetic neurons compared to myocytes was confirmed by a larger {sup 11}C-HED defect with a corresponding histologically identified region of denervation. Furthermore, partial reinnervation was observed in the chronic phase as shown by recovery of subepicardial {sup 11}C-HED uptake. (orig.)

Evaluation of myocardial sympathetic nerve function in patients with mitral valve prolapse using iodine-123-metaiodobenzylguanidine myocardial scintigraphy

International Nuclear Information System (INIS)

Kishi, Fumiko; Nomura, Masahiro; Yukinaka, Michiko

1996-01-01

Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve function. This study evaluated the presence of impaired myocardial sympathetic nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in nine patients with MVP. For comparison, 15 healthy subjects without heart disease were investigated (control group). Single photon emission computed tomography (SPECT) and anterior planar myocardial scintigraphy were performed 15 min (initial images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M) on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors of all oblique slices along the short-axis was calculated. The washout rates were higher at the inferoposterior and septal segments in patients with anterior leaflet prolapse, and at inferoposterior and lateral segments in patients with posterior leaflet prolapse. The bull's eye map showed increased washout rate in the apical and posteroseptal basal segments. There was no significant difference in the H/M ratio between MVP patients and the control group. These results indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve function in MVP. (author)

A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

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Fu, Liang-Wu; Longhurst, John C

2010-12-01

Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

Sympathetic rhythms and nervous integration.

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Gilbey, Michael P

2007-04-01

1. The present review focuses on some of the processes producing rhythms in sympathetic nerves influencing cardiovascular functions and considers their potential relevance to nervous integration. 2. Two mechanisms are considered that may account for rhythmic sympathetic discharges. First, neuronal elements of peripheral or central origin produce rhythmic activity by phasically exciting and/or inhibiting neurons within central sympathetic networks. Second, rhythms arise within central sympathetic networks. Evidence is considered that indicates the operation of both mechanisms; the first in muscle and the second in skin sympathetic vasoconstrictor networks. 3. Sympathetic activity to the rat tail, a model for the nervous control of skin circulation, is regulated by central networks involved in thermoregulation and those associated with fear and arousal. In an anaesthetized preparation, activity displays an apparently autonomous rhythm (T-rhythm; 0.4-1.2 Hz) and the level of activity can be manipulated by regulating core body temperature. This model has been used to study rhythm generation in central sympathetic networks and possible functional relevance. 4. A unique insight provided by the T rhythm, into possible physiological function(s) underlying rhythmic sympathetic discharges is that the activity of single sympathetic post-ganglionic neurons within a population innervating the same target can have different rhythm frequencies. Therefore, the graded and dynamic entrainment of the rhythms by inputs, such as central respiratory drive and/or lung inflation-related afferent activity, can produce graded and dynamic synchronization of sympathetic discharges. The degree of synchronization may influence the efficacy of transmission in a target chain of excitable cells. 5. The T-rhythm may be generated within the spinal cord because the intrathecal application of 5-hydroxytryptamine at the L1 level of the spinal cord of a rat spinalized at T10-T11 produces a T-like rhythm

NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure.

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Kinsman, Brian J; Browning, Kirsteen N; Stocker, Sean D

2017-09-15

Changes in extracellular osmolarity stimulate thirst and vasopressin secretion through a central osmoreceptor; however, central infusion of hypertonic NaCl produces a greater sympathoexcitatory and pressor response than infusion of hypertonic mannitol/sorbitol. Neurons in the organum vasculosum of the lamina terminalis (OVLT) sense changes in extracellular osmolarity and NaCl. In this study, we discovered that intracerebroventricular infusion or local OVLT injection of hypertonic NaCl increases lumbar sympathetic nerve activity, adrenal sympathetic nerve activity and arterial blood pressure whereas equi-osmotic mannitol/sorbitol did not alter any variable. In vitro whole-cell recordings demonstrate the majority of OVLT neurons are responsive to hypertonic NaCl or mannitol. However, hypertonic NaCl stimulates a greater increase in discharge frequency than equi-osmotic mannitol. Intracarotid or intracerebroventricular infusion of hypertonic NaCl evokes a greater increase in OVLT neuronal discharge frequency than equi-osmotic sorbitol. Collectively, these novel data suggest that subsets of OVLT neurons respond differently to hypertonic NaCl versus osmolarity and subsequently regulate body fluid homeostasis. These responses probably reflect distinct cellular mechanisms underlying NaCl- versus osmo-sensing. Systemic or central infusion of hypertonic NaCl and other osmolytes readily stimulate thirst and vasopressin secretion. In contrast, central infusion of hypertonic NaCl produces a greater increase in arterial blood pressure (ABP) than equi-osmotic mannitol/sorbitol. Although these responses depend on neurons in the organum vasculosum of the lamina terminalis (OVLT), these observations suggest OVLT neurons may sense or respond differently to hypertonic NaCl versus osmolarity. The purpose of this study was to test this hypothesis in Sprague-Dawley rats. First, intracerebroventricular (icv) infusion (5 μl/10 min) of 1.0 m NaCl produced a significantly greater

Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

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Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

2016-08-26

Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

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Lansdown, Andrew; Rees, D Aled

2012-12-01

Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

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JOSIANE CAMPOS CRUZ

2015-12-01

Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

Median Sacral Artery, Sympathetic Nerves, and the Coccygeal Body: A Study Using Serial Sections of Human Embryos and Fetuses.

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Jin, Zhe Wu; Cho, Kwang Ho; Jang, Hyung Suk; Murakami, Gen; Rodríguez-Vázquez, Jose Francisco

2016-07-01

To examine how the median sacral artery (MSA) is involved with the coccygeal body or glomus coccygeum, we studied serial frontal or sagittal sections of 14 embryos (approximately 5-6 weeks of gestation) and 12 fetuses (10-18 weeks). At five weeks, the caudal end of the dorsal aorta (i.e., MSA) accompanied putative sympathetic ganglion cells in front of the upper coccygeal and lower sacral vertebrae. At six weeks, a candidate for the initial coccygeal body was identified as a longitudinal arterial plexus involving nerve fibers and sympathetic ganglion cells between arteries. At 10-18 weeks, the MSA exhibited a highly tortuous course at the lower sacral and coccygeal levels, and was attached to and surrounded by veins, nerve fibers, and sympathetic ganglion cells near and between the bilateral origins of the levator ani muscle. Immunohistochemistry demonstrated expression of tyrosine hydroxylase and chromogranin A in the nerves. However, throughout the stages examined, we found no evidence suggestive of an arteriovenous anastomosis, such as well-developed smooth muscle. An acute anterior flexure of the vertebrae at the lower sacrum, as well as regression of the secondary neural tube, seemed to induce arterial plexus formation from an initial straight MSA. Nerves and ganglion cells were likely to be secondarily involved with the plexus because of the close topographical relationship. However, these nerves might play a major role in the extreme change into adult morphology. An arteriovenous anastomosis along the MSA might be an overinterpretation, at least in the prenatal human. Anat Rec, 299:819-827, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

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Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension.

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Li, De-Pei; Zhou, Jing-Jing; Zhang, Jixiang; Pan, Hui-Lin

2017-11-01

NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats. The basal amplitude of evoked NMDAR-EPSCs and puff NMDA currents in retrogradely labeled PVN neurons were significantly higher in SHRs than in WKY rats. The CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP) normalized the increased amplitude of NMDAR-EPSCs and puff NMDA currents in labeled PVN neurons in SHRs but had no effect in WKY rats. Treatment with AIP also normalized the higher frequency of NMDAR-mediated miniature EPSCs of PVN neurons in SHRs. CaMKII-mediated phosphorylation level of GluN2B serine 1303 (S1303) in the PVN, but not in the hippocampus and frontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased level of phosphorylated GluN2B S1303 in the PVN. In addition, microinjection of AIP into the PVN significantly reduced arterial blood pressure and lumbar sympathetic nerve discharges in SHRs. Our findings suggest that CaMKII activity is increased in the PVN and contributes to potentiated presynaptic and postsynaptic NMDAR activity to elevate sympathetic vasomotor tone in hypertension. SIGNIFICANCE STATEMENT Heightened sympathetic vasomotor tone is a major contributor to the development of hypertension. Although glutamate NMDA receptor (NMDAR)-mediated excitatory drive in the hypothalamus plays a critical role in increased sympathetic output in hypertension, the molecular mechanism involved in

Highly localized interactions between sensory neurons and sprouting sympathetic fibers observed in a transgenic tyrosine hydroxylase reporter mouse

Directory of Open Access Journals (Sweden)

Zhang Jun-Ming

2011-07-01

Full Text Available Abstract Background Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes. Results After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71% and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity. Conclusions The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing.

Sympathetic block by metal clips may be a reversible operation

DEFF Research Database (Denmark)

Thomsen, Lars L; Mikkelsen, Rasmus T; Derejko, Miroslawa

2014-01-01

, but the question of reversibility remains controversial. Two recent experimental studies found severe histological signs of nerve damage 4-6 weeks after clip removal, but they only used conventional histopathological staining methods. METHODS: Thoracoscopic clipping of the sympathetic trunk was performed in adult...... the sympathetic chain vary tremendously. Most surgeons transect or resect the sympathetic chain, but application of a metal clip that blocks transmission of nerve impulses in the sympathetic chain is used increasingly worldwide. This approach offers potential reversibility if patients regret surgery...... suggests in theory that application of metal clips to the sympathetic chain is a reversible procedure if only the observation period is prolonged. Further studies with longer periods between application and removal as well as investigations of nerve conduction should be encouraged, because we do not know...

Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

Energy Technology Data Exchange (ETDEWEB)

Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. (Indiana Univ. School of Medicine, IN (USA))

1989-11-15

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Clinical usefulness of 123I-metaiodobenzylguanidine myocardial scintigraphy in diabetic patients with cardiac sympathetic nerve dysfunction

International Nuclear Information System (INIS)

Miyanaga, Hajime; Yoneyama, Satoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru; Kunishige, Hiroshi

1995-01-01

To assess the clinical utility of 123 I-metaiodobenzylguanidine (MIBG) scintigraphy in evaluating cardiac sympathetic nerve disturbance in diabetic patients, we performed MIBG scintigraphy in 18 diabetic patients and 11 normal controls. Diabetic patients with symptomatic neuropathy (DM2) had a significantly lower heart to mediastinum uptake ratio than did those without neuropathy or normal controls in initial and delayed images (initial image, 1.90±0.27 vs 2.32±0.38, 2.41±0.40, p<0.01; delayed image, 1.80±0.31 vs 2.48±0.35, 2.56±0.28, p<001, respectively). Defect score, assessed visually, were higher in DM2 patients than in patients in the other two groups (initial image, 7±2.6 vs 1.5±1.9, 0.7±0.9; delayed image 10.6±3.3 vs 4.0±2.5, 1.7±1.6 p<0.01, respectively). The maximum washout rate in DM2 patients was also higher than those in patients in the other two groups. The findings of these indices obtained from MIBG scintigraphy coincided with the % low-frequency power extracted from heart rate fluctuations using a power spectral analysis and the results of the Schellong test, which were used to evaluate sympathetic function. These results suggest that MIBG scintigraphy may be useful for evaluating cardiac sympathetic nerve disturbance in patients with diabetes. (author)

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Directory of Open Access Journals (Sweden)

Yoshiki Shionoya

Full Text Available This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Science.gov (United States)

Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

2017-01-01

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

Science.gov (United States)

2012-04-26

Surgical Research, Fort Sam Houston, TX, USA 2 Department of Health and Kinesiology , The University of Texas at San Antonio, San Antonio, TX, USA Edited...suggested that this phenomenon may represent sympathetic baroreflex deafferentation (Cooke et al., 2009), as the fused bursts observed during intense ...Convertino, V. A. (2009). Muscle sympathetic nerve activity during intense lower body negative pressure to presyn- cope in humans. J. Physiol. (Lond

Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

Science.gov (United States)

Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

2015-02-01

Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

Science.gov (United States)

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Usefulness of cardiac 125I-metaiodobenzylguanidine uptake for evaluation of cardiac sympathetic nerve abnormalities in diabetic rats

International Nuclear Information System (INIS)

Abe, Nanami; Kashiwagi, Atsunori; Shigeta, Yukio

1992-01-01

We investigated cardiac sympathetic nerve abnormalities in streptozocin-induced diabetic rats using 125 I-metaiodobenzylguanidine (MIBG). The radioactivity ratio of cardiac tissue to 1 ml blood (H/B) was used as an index of cardiac MIBG uptake. Cardiac 125 I-MIBG uptake (H/B) in 4-, 8- and 20-wk diabetic rats was 48% lower than that in control rats. Similar results were obtained even when the data were corrected for g wet tissue weight. Although there was no improvement in H/B following 2-wk insulin treatment, the H/B ratio increased significantly, to 85% of control levels, following 4 wk insulin treatment indicating the reversibility of impaired MIBG uptake in diabetic rats. In vivo reserpine treatment resulted in a 50% reduction in the H/B value in control rats. However, the treatment did not significantly suppress uptake in diabetic rats. Cardiac norepinephrine content in both * 4- and ** 8-wk diabetic rats was significantly ( * p ** p 125 I-MIBG in diabetic rats is significantly impaired due to cardiac sympathetic nerve abnormalities. These abnormalities are reversible, however, dependent on the diabetic state. (author)

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

Science.gov (United States)

Sata, Yusuke; Head, Geoffrey A; Denton, Kate; May, Clive N; Schlaich, Markus P

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study

International Nuclear Information System (INIS)

Yulin He; Weina Zhou; Xiangcheng Wang; Baoliang Bao; Guojian Zhang; Cheng Wang; Chunmei Wang; Xuemei Wang; Wei Fang

2014-01-01

In this study, we synthesized and characterized N-[ 11 C]methyl-dopamine ([ 11 C]MDA) for cardiac sympathetic nerve imaging. [ 11 C]MDA was synthesized by direct N-methylation of dopamine with [ 11 C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [ 11 C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [ 11 C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [ 11 C]MDA had high myocardium uptake. PET/CT imaging showed [ 11 C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [ 11 C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging. (author)

Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

Science.gov (United States)

Nelles, E; Bützler, C; Jung, D; Temme, A; Gabriel, H D; Dahl, U; Traub, O; Stümpel, F; Jungermann, K; Zielasek, J; Toyka, K V; Dermietzel, R; Willecke, K

1996-09-03

The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mobilization from glycogen stores, when compared with wild-type liver. Thus, connexin32-containing gap junctions are essential in mouse liver for maximal intercellular propagation of the noradrenaline signal from the periportal (upstream) area, where it is received from sympathetic nerve endings, to perivenous (downstream) hepatocytes. In connexin32-defective liver, the amount of connexin26 protein expressed was found to be lower than in wild-type liver, and the total area of gap junction plaques was approximately 1000-fold smaller than in wild-type liver. In contrast to patients with connexin32 defects suffering from X chromosome-linked Charcot-Marie-Tooth disease (CMTX) due to demyelination in Schwann cells of peripheral nerves, connexin32-deficient mice did not show neurological abnormalities when analyzed at 3 months of age. It is possible, however, that they may develop neurodegenerative symptoms at older age.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

Directory of Open Access Journals (Sweden)

Yusuke Sata

2018-03-01

Full Text Available The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Device-based approaches for renal nerve ablation for hypertension and beyond

Directory of Open Access Journals (Sweden)

Alicia Ann Thorp

2015-07-01

Full Text Available Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy’s efficacy. Disrupting renal afferent sympathetic signalling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic over-activity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of–concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic over-activity is also presented.

Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression.

Science.gov (United States)

Garvin, Nathan M; Levine, Benjamin D; Raven, Peter B; Pawelczyk, James A

2014-01-01

Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure-raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose-dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The ABD inflation also caused a significant decrease in stroke volume (-11 ± 3 and -10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.

Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

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Yumie Morimoto-Kobayashi

Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve.

Science.gov (United States)

Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Kamiya, Atsunori; Shishido, Toshiaki; Sugimachi, Masaru

2018-03-01

Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension

NARCIS (Netherlands)

van Brussel, Peter M.; Eeftinck Schattenkerk, Daan W.; Dobrowolski, Linn C.; de Winter, Robbert J.; Reekers, Jim A.; Verberne, Hein J.; Vogt, Liffert; van den Born, Bert-Jan H.

2016-01-01

Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity

Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

NARCIS (Netherlands)

Oey, P.L.; Vos, P.E.; Wieneke, G.H.; Wokke, J.H.J.; Blankestijn, P.J.; Karemaker, J.M.

2002-01-01

The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis

NARCIS (Netherlands)

Oey, P. Liam; Vos, Pieter E.; Wieneke, George H.; Wokke, John H. J.; Blankestijn, Peter J.; Karemaker, John M.

2002-01-01

The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

Sympathetic chain Schwannoma

International Nuclear Information System (INIS)

Al-Mashat, Faisal M.

2009-01-01

Schwannomas are rare, benign, slowly growing tumors arising from Schwann cells that line nerve sheaths. Schwannomas arising from the cervical sympathetic chain are extremely rare. Here, we report a case of a 70-year-old man who presented with only an asymptomatic neck mass. Physical examination revealed a left sided Horner syndrome and a neck mass with transmitted pulsation and anterior displacement of the carotid artery. Computed tomography (CT) showed a well-defined non-enhancing mass with vascular displacement. The nerve of origin of this encapsulated tumor was the sympathetic chain. The tumor was excised completely intact. The pathologic diagnosis was Schwannoma (Antoni type A and Antoni type B). The patient has been well and free of tumor recurrence for 14 months with persistence of asymptomatic left sided Horner syndrome. The clinical, radiological and pathological evaluations, therapy and postoperative complications of this tumor are discussed. (author)

Effect of nerve activity on transport of nerve growth factor and dopamine β-hydroxylase antibodies in sympathetic neurones

International Nuclear Information System (INIS)

Lees, G.; Chubb, I.; Freeman, C.; Geffen, L.; Rush, R.

1981-01-01

The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine β-hydroxylase (DBH) antibodies was studied by injecting 125 I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

Science.gov (United States)

van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

2016-03-01

Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata

Science.gov (United States)

Marina, Nephtali; Abdala, Ana P.L.; Korsak, Alla; Simms, Annabel E.; Allen, Andrew M.; Paton, Julian F.R.; Gourine, Alexander V.

2011-01-01

Aims Increased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses. Methods and results In anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor. In anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO2-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity. Conclusion These data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO2. PMID:21543384

Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

OpenAIRE

Nelles, E; Bützler, C; Jung, D; Temme, A; Gabriel, H D; Dahl, U; Traub, O; Stümpel, F; Jungermann, K; Zielasek, J; Toyka, K V; Dermietzel, R; Willecke, K

1996-01-01

The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mob...

Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN

Science.gov (United States)

Bardgett, Megan E.; Chen, Qing-Hui; Guo, Qing; Calderon, Alfredo S.; Andrade, Mary Ann

2014-01-01

Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-d-aspartate (NMDA) receptors reduced (P dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases. PMID:24671240

Abnormal sympathetic nerve activity in women exposed to cigarette smoke: a potential mechanism to explain increased cardiac risk.

Science.gov (United States)

Middlekauff, Holly R; Park, Jeanie; Agrawal, Harsh; Gornbein, Jeffrey A

2013-11-15

In women, cardiac deaths attributable to tobacco exposure have reached the same high levels as men. Normally, sympathetic nerve activity (SNA) fluctuates according to the menstrual phase, but in habitual smokers, SNA levels remain constant. Our purpose is to extend these observations to other groups of women exposed to tobacco smoke and to explore potential mechanisms. We hypothesize that women exposed to secondhand smoke, but not former smokers, have nonfluctuating SNA compared with never smokers, and that impaired baroreflex suppression of SNA, and/or heightened central SNA responses, underlie this nonfluctuating SNA. We also hypothesize that female smokers have impaired nocturnal blood pressure dipping, normally mediated by modulation of SNA. In 49 females (19 never, 12 current, 9 former, 9 passive smokers), SNA was recorded (microneurography) during high- and low-hormone ovarian phases at rest, during pharmacological baroreflex testing, and during the cold pressor test (CPT). Twenty-four hour blood pressure (BP) monitoring was performed. Current and passive smokers, but not former smokers, had a nonfluctuating pattern of SNA, unlike never smokers in whom SNA varied with the menstrual phase. Baroreflex control of SNA was significantly blunted in current smokers, independent of menstrual phase. In passive smokers, SNA response to CPT was markedly increased. Nondipping was unexpectedly high in all groups. SNA does not vary during the menstrual cycle in active and passive smokers, unlike never and former smokers. Baroreflex control of SNA is blunted in current smokers, whereas SNA response to CPT is heightened in passive smokers. Smoking cessation is associated with return of the altered SNA pattern to normal.

CT-clinical approach to patients with symptoms related to the V, VII, IX-XII cranial nerves and cervical sympathetics

International Nuclear Information System (INIS)

Kalovidouris, A.; Mancuso, A.A.; Dillon, W.

1984-01-01

Forty-three patients who had signs and symptoms possibly related to the extracranial course of cranial nerves V, VII, IX, X-XII, and the cervical sympathetics were examined prospectively using high resolution CT to obtain images of thin sections during rapid drip infusion of contrast material. Anatomic areas in the scan protocols included the posterior fossa, cavernous and paranasal sinuses, skull base, temporal bone, nasopharynx, parotid gland, tongue base, and neck. Nine of the 23 patients with possible fifth nerve deficits had extracranial structural lesions that explained the symptoms; none of these nine, however, had typical trigeminal neuralgia. Of eight patients with peripheral seventh nerve abnormalities, two had positive findings on scans. Of five patients presenting with referred ear pain, three had carcinoma of the upper aerodigestive tract. The authors' experience suggests that patients at high risk for structural lesions responsible for cranial nerve deficits can be selected by clinical criteria. Protocols for each clinical setting are presented

Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

Science.gov (United States)

Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

2014-12-01

Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sympathetic skin responses in patients with hyperthyroidism.

Science.gov (United States)

Gozke, E; Ozyurt, Z; Dortcan, N; Ore, O; Kocer, A; Ozer, E

2007-01-01

The aim of this study was to investigate the disorders of sympathetic nervous system in patients with hyperthyroidism using sympathetic skin response (SSR). Twenty-two newly diagnosed cases with hyperthyroidism were included in the study. The results were compared with those of 20 healthy controls. SSR was recorded with the contralateral electrical stimulation of the median nerve (of the upper extremities) and tibial nerve (of the lower extremities) with active electrodes placed on palms and soles and reference electrodes attached on the dorsal aspects of hands and feet. Ages of the cases with hyperthyroidism and controls ranged between 15-65 years (mean: 46.7 +/- 15.0 years) and 24-62 years (mean: 39.6 +/- 9.8 years) respectively (p > 0.05). In all the control subjects SSR could be obtained, while from the lower extremities of 4 cases with hyperthyroidism (18.0%) SSR could not be elicited. Mean SSR latencies of lower extremities were found significantly longer than control group (p nervous system involvement in cases with hyperthyroidism.

α-Amylase as a reliable and convenient measure of sympathetic activity: don't start salivating just yet!

Science.gov (United States)

Bosch, Jos A; Veerman, Enno C I; de Geus, Eco J; Proctor, Gordon B

2011-05-01

Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which provides a simple means of quantification by measuring its enzymatic activity. This commentary will address a number of common misconceptions and methodological issues that surround the use of sAA as a marker of SNS activity and limit its utility in biobehavioral research. The usefulness of sAA as an SNS marker is undermined by the fact that the parasympathetic nerves also play a significant role in sAA release. Local parasympathetic nerves regulate sAA activity via: (1) α-amylase release from glands that are solely or mainly parasympathetically innervated; (2) via synergistic sympathetic-parasympathetic effects on protein secretion (known as 'augmented secretion'); and (3) via effects on salivary flow rate. Regarding methodology, we discuss why it is problematic: (1) to ignore the contribution of salivary flow rate; (2) to use absorbent materials for saliva collection, and; (3) to stimulate saliva secretion by chewing. While these methodological problems can be addressed by using standardized and timed collection of unstimulated saliva, the physiological regulation of sAA secretion presents less resolvable issues. We conclude that at present there is insufficient support for the use and interpretation of sAA activity as a valid and reliable measure of SNS activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Baroreflex control of sympathetic activity in experimental hypertension

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M.C.C. Irigoyen

1998-09-01

Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.

Science.gov (United States)

Y-Hassan, Shams; De Palma, Rodney

2017-02-01

Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity, is characterized by a unique pattern of circumferential and typically regional left ventricular wall motion abnormality resulting in a conspicuous transient ballooning of the left ventricle during systole. The mechanism of the disease remains elusive. However, the sudden onset of acute myocardial stunning in a systematic pattern extending beyond a coronary artery territory; the history of a preceding emotional or physical stress factor in two thirds of cases; the signs of sympathetic denervation at the regions of left ventricular dysfunction on sympathetic scintigraphy; the finding of myocardial edema and other signs consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic resonance imaging; and the contraction band necrosis on histopathological examination all argue strongly for the involvement of the cardiac sympathetic nervous system in the pathogenesis of TS. In this narrative review, extensive evidence in support of local cardiac sympathetic nerve hyperactivation, disruption and norepinephrine spillover causing TS in predisposed patients is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

Energy Technology Data Exchange (ETDEWEB)

Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke [Nihon Univ., Tokyo (Japan). School of Medicine

2000-12-01

Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5{+-}6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33{+-}0.22 in chronic heart failure class I, 2.50{+-}0.34 in class II, 1.95{+-}0.61 in class III, and 1.39{+-}0.29 in class IV (p<0.05). %WR was 24.8{+-}12.8% in chronic heart failure class I, 23.3{+-}10.2% in class II, 49.2{+-}24.5% in class III, and 66.3{+-}26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

Netrin-1 controls sympathetic arterial innervation.

Science.gov (United States)

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-07-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Device-based approaches for renal nerve ablation for hypertension and beyond

Science.gov (United States)

Thorp, Alicia A.; Schlaich, Markus P.

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented. PMID:26217232

Device-based approaches for renal nerve ablation for hypertension and beyond.

Science.gov (United States)

Thorp, Alicia A; Schlaich, Markus P

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

Directory of Open Access Journals (Sweden)

Heung Yong Jin

2015-12-01

Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

Effect of amine uptake inhibitors on the uptake of 14C-bretylium in intact and degenerating sympathetic nerves of the rat

International Nuclear Information System (INIS)

Almgren, O.

1981-01-01

The effect of different amine uptake inhibitors on the accumulation of 14 C-bretylium in sympathetically denervated or decentralized salivary glands were studied in vivo in rats 11-14 hours after the surgical intervention. The time period chosen is known to be critical for the delaying effect of bretylium on the degeneration transmitter release in sympathetically innervated organs. Cocaine, desmethylimipramine (DMI), protriptyline or reserpine all depressed the uptake of 14 C-bretylium in both denervated and decentralized salivary glands, cocaine being the most efficient one. DMI and protriptyline, but not cocaine inhibit the degeneration delaying effect of bretylium, while all three agents inhibit amine uptake at level of the nerve cell membrane. Apparently, bretylium reaches the critical sites of its degeneration delaying action by the axonal amine pump but only a small fraction of the drug entering the degenerating adrenergic nerve terminal is needed at the critical sites to interact with the degeneration processes. The difference between the tricyclic antidepressants on one hand and cocaine on the other with respect to the effect on the degeneration delaying action of bretylium, must depend on some action different from the axonal membrane uptake inhibition. Reserpine which is known not to interfere with the delaying effect of bretylium on the denervation degeneration did reduce the uptake of 14 C-bretylium. This fact seems to indicate that the site of action of bretylium is located outside the adrenergic nerve granules. (author)

Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

International Nuclear Information System (INIS)

Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke

2000-01-01

Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5±6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33±0.22 in chronic heart failure class I, 2.50±0.34 in class II, 1.95±0.61 in class III, and 1.39±0.29 in class IV (p<0.05). %WR was 24.8±12.8% in chronic heart failure class I, 23.3±10.2% in class II, 49.2±24.5% in class III, and 66.3±26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

Implantable electrode for recording nerve signals in awake animals

Science.gov (United States)

Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

1976-01-01

An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

The role of the renal afferent and efferent nerve fibres in heart failure

Directory of Open Access Journals (Sweden)

Lindsea C Booth

2015-10-01

Full Text Available Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibres. In heart failure (HF there is an increase in renal sympathetic nerve activity, which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibres, afferent renal nerve fibres, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

The role of the renal afferent and efferent nerve fibers in heart failure

Science.gov (United States)

Booth, Lindsea C.; May, Clive N.; Yao, Song T.

2015-01-01

Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study.

Science.gov (United States)

Atherton, Daniel S; Deep, Nicholas L; Mendelsohn, Farrell O

2012-07-01

Hypertension remains an epidemic uncontrolled with pharmacologic therapies. A novel catheter inserted into the renal artery has been shown to lower blood pressure by ablating the renal sympathetic nerves with radiofrequency energy delivered through the arterial wall. We report a histologic study describing the anatomic substrate for this technique, specifically the renal sympathetic nervous system. Histological sections from proximal, middle, and distal renal artery segments from nine renal arteries (five human autopsies) were analyzed. Nerves were manually counted and their distance from the lumen-intima interface was measured using a micrometer. The nerves were then categorized by location into 0.5-mm-wide "rings" that were arranged circumferentially around the renal artery lumen. Of all nerves detected, 1.0% was in the 0-0.5 mm ring, 48.3% were in the 0.5-1.0 mm ring, 25.6% were in the 1.0-1.5 mm ring, 15.5% were in the 1.5-2.0 mm ring, and 9.5% were in the 2.0-2.5 mm ring. Beyond 0.5 mm, the proportion of nerves tended to decrease as the distance from the lumen increased. Totally, 90.5% of all nerves in this study existed within 2.0 mm of the renal artery lumen. Additionally, the number of nerves tended to increase along the length of the artery from proximal to distal segments (proximal = 216; middle = 323; distal = 417). In conclusion, our analysis indicates that a great proportion of renal sympathetic nerves have close proximity to the lumen-intima interface and should thus be accessible via renal artery interventional approaches such as catheter ablation. This data provides important anatomic information for the development of ablation and other type devices for renal sympathetic denervation. © 2011 Wiley Periodicals, Inc.

Muscle afferent receptors engaged in augmented sympathetic responsiveness in peripheral artery disease

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Jianhua eLi

2012-07-01

Full Text Available The exercise pressor reflex (EPR is a neural control mechanism responsible for the cardiovascular responses to exercise. As exercise is initiated, thin fiber muscle afferent nerves are activated by mechanical and metabolic stimuli arising in the contracting muscles. This leads to reflex increases in arterial blood pressure and heart rate primarily through activation of sympathetic nerve activity (SNA. Studies of humans and animals have indicated that the EPR is exaggerated in a number of cardiovascular diseases. For the last several years, studies have specifically employed a rodent model to examine the mechanisms at receptor and cellular levels by which responses of SNA and blood pressure to static exercise are heightened in peripheral artery disease (PAD, one of the most common cardiovascular disorders. A rat model of this disease has well been established. Specifically, femoral artery occlusion is used to study intermittent claudication that is observed in human PAD. The receptors on thin fiber muscle afferents that are engaged in this disease include transient receptor potential vanilloid type 1 (TRPV1, purinergic P2X and acid sensing ion channel (ASIC. The role played by nerve growth factor (NGF in regulating those sensory receptors in the processing of amplified EPR was also investigated. The purpose of this review is to focus on a theme namely that PAD accentuates autonomic reflex responses to exercise and further address regulatory mechanisms leading to abnormal sympathetic responsiveness. This review will present some of recent results in regard with several receptors in muscle sensory neurons in contribution to augmented autonomic reflex responses in PAD. Review of the findings from recent studies would lead to a better understanding in integrated processing of sympathetic nervous system in PAD.

Sympathetic responses during saline infusion into the veins of an occluded limb.

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Cui, Jian; McQuillan, Patrick; Moradkhan, Raman; Pagana, Charles; Sinoway, Lawrence I

2009-07-15

Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 +/- 1.2 bursts min(-1)), MSNA increased significantly during the saline infusion (22.5 +/- 2.6 bursts min(-1), P Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.

Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

Energy Technology Data Exchange (ETDEWEB)

Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi, Gunma (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Department of Internal Medicine, Gunma (Japan)

2005-08-01

The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33{+-}7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39{+-}10 to 34{+-}9 (P<0.01), H/M ratios increased from 1.62{+-}0.27 to 1.76{+-}0.29 (P<0.01), WR decreased from 50{+-}14% to 42{+-}14% (P<0.05) and plasma BNP concentrations decreased from 226{+-}155 to 141{+-}90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180{+-}30 to 161{+-}30 ml (P<0.05) and the LVESV decreased from 122{+-}35 to 105{+-}36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33{+-}8% to 36{+-}12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, {sup 123}I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms

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Jasdeep Kaur

2017-08-01

Full Text Available The incidence of chronic kidney disease (CKD is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.

Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

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Abdulla, M H; Duff, M; Swanton, H; Johns, E J

2016-11-01

This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

SYMPATHETIC NEURAL AND HEMODYNAMIC RESPONSES DURING COLD PRESSOR TEST IN ELDERLY BLACKS AND WHITES

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Okada, Yoshiyuki; Jarvis, Sara S.; Best, Stuart A.; Edwards, Jeffrey G.; Hendrix, Joseph M.; Adams-Huet, Beverley; Vongpatanasin, Wanpen; Levine, Benjamin D.; Fu, Qi

2016-01-01

The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Since blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate (HR), cardiac output (Qc), and muscle sympathetic nerve activity (MSNA) were measured during supine baseline, 2-min CPT, and 3-min recovery in 47 elderly [68±7 (SD) yrs] volunteers (12 blacks, 35 whites). Baseline BP, HR, Qc, or MSNA did not differ between races. Systolic and diastolic BP (DBP) and HR increased during CPT (all P0.05). Qc increased during CPT and up to 30 sec of recovery in both groups, but was lower in blacks than whites. MSNA increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, while the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in DBP was correlated with Δ total activity at 1 min into CPT in both blacks (r=0.78, P=0.003) and whites (r=0.43, P=0.009), while the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (e.g., Qc) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), and/or enhanced non-adrenergically mediated vasoconstriction in elderly blacks. PMID:27021009

Vagal nerve stimulation therapy: what is being stimulated?

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Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Vagal nerve stimulation therapy: what is being stimulated?

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Guy Kember

Full Text Available Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Transient sixth cranial nerve palsy following orgasm abrogated by treatment with sympathomimetic amines.

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Check, J H; Katsoff, B

2014-01-01

To describe a unique disorder where a transient 6th nerve palsy leading to diploplia following orgasm developed in a 28-year-old woman. This coincided with a weight gain of 100 pounds in a short time without a corresponding change in dietary habits. She was treated with the sympathomimetic amine dextroamphetamine sulfate. Indeed she immediately responded to treatment with dextroamphetamine sulfate sustained release capsules with complete resolution of the episodes of 6th nerve palsy following orgasm. The main importance of this case is that it suggests that orgasm causes a transient generalized decrease in sympathetic nervous system activity and that the achievement of an orgasm may require an increase in the sympathetic nervous system activity.

Renal sympathetic nervous system and the effects of denervation on renal arteries.

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Kannan, Arun; Medina, Raul Ivan; Nagajothi, Nagapradeep; Balamuthusamy, Saravanan

2014-08-26

Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal- as well as systemic- level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements. Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

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Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

2016-10-01

We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

Functional Nerve Preservation in Extracranial Head and Neck Schwannoma Surgery.

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Ijichi, Kei; Kawakita, Daisuke; Maseki, Shinichiro; Beppu, Shintaro; Takano, Gaku; Murakami, Shingo

2016-05-01

A schwannoma is an uncommon, benign neurogenic tumor of Schwann cells. Tumor enucleation is the recommended surgical method to preserve function of the original nerve, although enucleation does not guarantee completely intact nerve function after the operation. To establish a strategy for functional preservation in extracranial head and neck schwannoma treatment by using an electromyographic (EMG) system during tumor resection. A retrospective cohort study was conducted of 15 patients who underwent surgery for removal of schwannoma tumors between April 1, 2006, and March 31, 2015, at an academic tertiary referral center. Data analysis was conducted from April 3, 2006, to September 15, 2015. Neurogenic tumors were diagnosed according to preoperative findings, and during surgery tumors were exposed and given EMG-controlled electrical stimulation to analyze their origins. In motor nerve cases, the electrical activity of the muscle was measured and recorded by EMG. The tumor was then enucleated by incision along tumor fibers mapped using EMG stimulation. If a nerve bundle was visible, we incised along there and enucleated the tumor. A strategy using electrical stimulation to improve preservation of nerve function in extracranial head and neck schwannoma operations. Frequency and duration of postoperative neurologic complications associated with functional preservation surgery with tumor enucleation was evaluated using EMG monitoring according to tumor origin. Of the 15 patients with extracranial schwannoma, 9 (60%) were women (mean [SD] age, 36.3 [15.3] years). All 15 patients underwent surgery using a transcervical approach. The most common nerves of origin were the vagus nerve and the sympathetic chain. In sensory or sympathetic nerve cases, the EMG response was absent. Two of 5 patients with vagus schwannoma had postoperative temporary vocal nerve palsy. These symptoms showed improvement after 1 year. There was no tumor recurrence during the follow-up period in any

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling.

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Johnson, John M; Yen, Tony C; Zhao, Kun; Kosiba, Wojciech A

2005-04-01

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.

Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

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Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

2014-12-01

Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. Copyright © 2014 the American Physiological Society.

Transvenous stimulation of the renal sympathetic nerves increases systemic blood pressure: a potential new treatment option for neurocardiogenic syncope.

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Madhavan, Malini; Desimone, Christopher V; Ebrille, Elisa; Mulpuru, Siva K; Mikell, Susan B; Johnson, Susan B; Suddendorf, Scott H; Ladewig, Dorothy J; Gilles, Emily J; Danielsen, Andrew J; Asirvatham, Samuel J

2014-10-01

Neurocardiogenic syncope (NCS) is a common and sometimes debilitating disorder, with no consistently effective treatment. NCS is due to a combination of bradycardia and vasodilation leading to syncope. Although pacemaker devices have been tried in treating the bradycardic aspect of NCS, no device-based therapy exists to treat the coexistent vasodilation that occurs. The renal sympathetic innervation has been the target of denervation to treat hypertension. We hypothesized that stimulation of the renal sympathetic nerves can increase blood pressure and counteract vasodilation in NCS. High-frequency stimulation (800-900 pps, 10 V, 30-200 seconds) was performed using a quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant increase in blood pressure (BP; mean [SD] systolic BP 117 [±28] vs. 128 [±33], diastolic BP 75 [±19] vs. 87 [±29] mmHg) was noted during the stimulation, which returned to baseline after cessation of stimulation. The mean increase in systolic and diastolic BP was 13.0 (±3.3) (P = 0.006) and 10.2 (±4.6) (P = 0.08), respectively. We report the first ever study of feasibility and safety of high-frequency electrical stimulation of the renal sympathetic innervation to increase BP in animal models. This has potential applications in the treatment of hypotensive states such as NCS. © 2014 Wiley Periodicals, Inc.

Assessment of cardiac sympathetic nerve integrity with positron emission tomography

International Nuclear Information System (INIS)

Raffel, David M.; Wieland, Donald M.

2001-01-01

The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy

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Jianguo Cheng

2012-01-01

Full Text Available The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic blocks over a 26-month period provided sustained pain relief in his legs. Additional thoracic paravertebral blocks further provided control of the pain in the trunk which can occasionally be seen in severe diabetic neuropathy cases, consequent to extensive involvement of the intercostal nerves. These blocks provided sustained and significant pain relief and improvement of quality of life over a period of more than two years. We thus provided the first clinical evidence supporting the notion that sympathetic nervous system plays a critical role in painful diabetic neuropathy and sympathetic blocks can be an effective management modality of painful diabetic neuropathy. We concluded that the sympathetic nervous system is a valuable therapeutic target of pharmacological and interventional modalities of treatments in painful diabetic neuropathy patients.

Altered differential control of sympathetic outflow following sedentary conditions: Role of subregional neuroplasticity in the RVLM

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Madhan Subramanian

2016-07-01

Full Text Available Despite the classically held belief of an all-or-none activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA but not lumbar SNA (LSNA to activation of the rostral ventrolateral medulla (RVLM in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10-12 weeks on running wheels or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals.

The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

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Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

2015-04-20

What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia.

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Prabhakar, Nanduri R; Kumar, Ganesh K

2010-11-30

Sleep disordered breathing with recurrent apneas is one of the most frequently encountered breathing disorder in adult humans and preterm infants. Recurrent apnea patients exhibit several co-morbidities including hypertension and persistent sympathetic activation. Intermittent hypoxia (IH) resulting from apneas appears to be the primary stimulus for evoking autonomic changes. The purpose of this article is to briefly review the effects of IH on chemo- and baro-reflexes and circulating vasoactive hormones and their contribution to sympathetic activation and blood pressures. Sleep apnea patients and IH-treated rodents exhibit exaggerated arterial chemo-reflex. Studies on rodent models demonstrated that IH leads to hyperactive carotid body response to hypoxia. On the other hand, baro-reflex function is attenuated in patients with sleep apnea and in IH-treated rodents. Circulating vasoactive hormone levels are elevated in sleep apnea patients and in rodent models of IH. Thus, persistent sympathetic activation and hypertension associated with sleep apneas seems to be due to a combination of altered chemo- and baro-reflexes resulting in sympathetic activation and action of elevated circulating levels of vasoactive hormones on vasculature. Copyright © 2010 Elsevier B.V. All rights reserved.

Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects

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Carter, Jason R.; Ray, Chester A.; Downs, Emily M.; Cooke, William H.

2003-01-01

The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.

Deleterious effect of salusin-β in paraventricular nucleus on sympathetic activity and blood pressure via NF-κB signaling in a rat model of obesity hypertension.

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Huang, Xiaodong; Wang, Yanchun; Ren, Kuang

2015-08-01

The paraventricular nucleus (PVN) has been shown to play a critical role in regulating blood pressure and sympathetic activity in obesity hypertension (OH). Salusin-β is a bioactive peptide with potential roles in mediating cardiovascular activity. The study was designed to test the hypothesis that salusin-β in the PVN can modulate sympathetic activity and blood pressure in OH. Male Sprague-Dawley rats were used to induce OH by a 12-week feeding of a high-fat diet (42% kcal as fat). Microinjection of salusin-β into the PVN increased the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner, whereas salusin-β antibody elicited significant decreases in RSNA, MAP and HR, and abolished the effects of salusin-β only in the OH rats. As expected, the OH rats had a higher norepinephrine level, which was further increased by salusin-β. Furthermore, salusin-β in the PVN accelerated the nuclear translocation of the p65 subunit of nuclear factor kappa B (NF-KB) and the degradation of IKB-α (an endogenous inhibitor of NF-KB). Pretreatment with pyrrolidine dithiocarbamate (an exogenous inhibitor of NF-KB) decreased RSNA, MAP and HR, and abolished the effects of salusin-β in the PVN in the OH rats. We concluded that salusin-β in the PVN markedly increased sympathetic outflow and blood pressure in diet-induced OH rats via NF-κB signaling.

Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

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Xu, Bo; Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

2015-05-01

Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-D-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure. Copyright © 2015 the American Physiological Society.

Recruitment pattern of sympathetic muscle neurons during premature ventricular contractions in heart failure patients and controls.

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Maslov, Petra Zubin; Breskovic, Toni; Brewer, Danielle N; Shoemaker, J Kevin; Dujic, Zeljko

2012-12-01

Premature ventricular contractions (PVC) elicit larger bursts of multiunit muscle sympathetic nerve activity (MSNA), reflecting the ability to increase postganglionic axonal recruitment. We tested the hypothesis that chronic heart failure (CHF) limits the ability to recruit postganglionic sympathetic neurons as a response to PVC due to the excessive sympathetic activation in these patients. Sympathetic neurograms of sufficient signal-to-noise ratio were obtained from six CHF patients and from six similarly aged control individuals. Action potentials (APs) were extracted from the multiunit sympathetic neurograms during sinus rhythm bursts and during the post-PVC bursts. These APs were classified on the basis of the frequency per second, the content per burst, and the peak-to-peak amplitude, which formed the basis of binning the APs into active clusters. Compared with controls, CHF had higher APs per burst and higher number of active clusters per sinus rhythm burst (P < 0.05). Compared with sinus rhythm bursts, both groups increased AP frequency and the number of active clusters in the post-PVC burst (P < 0.05). However, compared with controls, the increase in burst integral, AP frequency, and APs per burst during the post-PVC burst was less in CHF patients. Nonetheless, the PVC-induced increase in active clusters per burst was similar between the groups. Thus, these CHF patients retained the ability to recruit larger APs but had a diminished ability to increase overall AP content.

Device-based approaches for renal nerve ablation for hypertension and beyond

OpenAIRE

Alicia Ann Thorp; Markus Peter Schlaich; Markus Peter Schlaich

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy...

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

Science.gov (United States)

Cui, Jian; McQuillan, Patrick M.; Blaha, Cheryl; Kunselman, Allen R.

2012-01-01

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. PMID:22707559

Effect of heat-killed Lactobacillus brevis SBC8803 on cutaneous arterial sympathetic nerve activity, cutaneous blood flow and transepidermal water loss in rats.

Science.gov (United States)

Horii, Y; Kaneda, H; Fujisaki, Y; Fuyuki, R; Nakakita, Y; Shigyo, T; Nagai, K

2014-05-01

To evaluate the efficacy of the effects of heat-killed Lactobacillus brevis SBC8803 (HK-SBC8803) on the standard physiological markers of skin health of cutaneous arterial sympathetic nerve activity (CASNA), cutaneous blood flow and transepidermal water loss (TEWL) and to determine whether SBC8803 targets serotonin 5-HT3 receptors in rats. A set of three experiments were conducted to examine the effects of SBC8803 on CASNA, cutaneous blood flow and TEWL using Wistar and hairless rats. Two additional experiments further attempted to determine whether HK-SBC8803 was targeting the serotonin 5-HT3 receptors by pretreatment with the 5-HT3 antagonist granisetron. Administration of HK-SBC8803 in the first three experiments caused marked inhibition of CASNA and significant elevation of cutaneous blood flow under urethane anaesthesia as well as significant decrease in TEWL on the dorsal skin of conscious hairless rats. Pretreatment with granisetron decreased the effects of HK-SBC8803 on CASNA and cutaneous blood flow. These findings suggest that HK-SBC8803 reduces CASNA, increases cutaneous blood flow and decreases TEWL and that 5-HT3 receptors may be involved in CASNA and cutaneous blood flow responses. HK-SBC8803 could be a useful substance in the treatment/prevention of skin problems, specifically chapped or dry skin. © 2014 The Society for Applied Microbiology.

Renal Sympathetic Denervation: Hibernation or Resurrection?

Science.gov (United States)

Papademetriou, Vasilios; Doumas, Michael; Tsioufis, Costas

The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research. © 2016 S. Karger AG, Basel.

The morphological substrate for Renal Denervation : Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study

NARCIS (Netherlands)

van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

2015-01-01

BACKGROUND: Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of

Effects of the α-adrenoceptor antagonists phentolamine, phenoxybenzamine, and Idazoxan on sympathetic blood flow control in the periodontal ligament of the cat

International Nuclear Information System (INIS)

Edwall, B.; Gazelius, B.

1988-01-01

Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of 125 I - during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ) or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three α-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the α 1 and α 2 subtypes in the sympathetic regulation of the blood flow in the PDL of the cat. A component of the response elicited by electrical sympathetic stimulation appeared to be resistant to α-adrenoceptor blockade. Administration of guanethidine (which inhibits further release of NA and neuropeptide Y) after PA abolished this residual sympathetic response

An implantable nerve cooler for the exercising dog.

Science.gov (United States)

Borgdorff, P; Versteeg, P G

1984-01-01

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy

International Nuclear Information System (INIS)

Koyama, Keiko; Inoue, Tomio; Hasegawa, Akira; Oriuchi, Noboru; Okamoto, Eiichi; Tomaru, Yumi; Endo, Keigo

2001-01-01

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p<0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p<0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r=0.80, p<0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart. (author)

Sympathetic Innervation during Development Is Necessary for Pancreatic Islet Architecture and Functional Maturation

Directory of Open Access Journals (Sweden)

Philip Borden

2013-07-01

Full Text Available Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion, and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in deinnervated animals. Furthermore, in neuron-islet cocultures, sympathetic neurons promoted islet cell migration in a β-adrenergic-dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders.

Increased Sympathetic Renal Innervation in Hemodialysis Patients Is the Anatomical Substrate of Sympathetic Hyperactivity in End-Stage Renal Disease.

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Mauriello, Alessandro; Rovella, Valentina; Anemona, Lucia; Servadei, Francesca; Giannini, Elena; Bove, Pierluigi; Anselmo, Alessandro; Melino, Gerry; Di Daniele, Nicola

2015-11-26

Renal denervation represents an emerging treatment for resistant hypertension in patients with end-stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach. The distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end-stage renal disease on dialysis (DIAL group) and 16 age-matched control nondialysis patients (CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri-adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm(2), P=0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm(2), P=0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history. The findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end-stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Release of NPY in pig pancreas: Dual parasympathetic and sympathetic regulation

International Nuclear Information System (INIS)

Sheikh, S.P.; Holst, J.J.; Skak-Nielsen, T.; Knigge, U.; Warberg, J.; Theodorsson-Norheim, E.; Hoekfelt, T.; Lundberg, J.M.; Schwartz, T.W.

1988-01-01

Several lines of evidence have connected neuropeptide Y (NPY), a 36-residue polypeptide, to the sympathetic division of the autonomic nervous system. The authors studied the localization, the molecular characteristics, and the release of NPY and norepinephrine (NE) in the porcine pancreas. Immunohistochemical investigations revealed that NPY nerves around blood vessels were likely to be of adrenergic nature, whereas NPY-immunoreactive fibers close to exocrine and endocrine cells may originate from local ganglia also containing VIP (vasoactive intestinal peptide) and PHI (peptide histidine isoleucine). Electrical stimulation of the splanchnic nerve supply to the isolated perfused pig pancreas resulted in a corelease of NPY and NE into the venous effluent. Stimulation of the vagal nerves caused a sevenfold larger release of NPY without affecting the NE secretion. Characterization of the NPY immunoreactivity in the pancreatic tissue and in the venous effluent by gel filtration, high-performance liquid chromatography, and isoelectric focusing shoed that the immunoreactive NPY was indistinguishable from synthetic porcine NPY. It is concluded that, although NPY is associated with sympathetic perivascular neurons, the majority of the pancreatic NPY-containing nerve fibers are likely to belong to the parasympathetic division of the autonomic nervous system

Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

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Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

2015-01-01

It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

Science.gov (United States)

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of experimental hyperinsulinemia on sympathetic nervous system activity in the rat

International Nuclear Information System (INIS)

Young, J.B.

1988-01-01

Since insulin acutely stimulates the sympathetic nervous system, a role for sympathetic overactivity has been hypothesized to underlie the association between chronic hyperinsulinemia and hypertension. To assess the effect of sustained hyperinsulinemia on sympathetic function, [ 3 H]norepinephrine (NE) turnover was measured in rats injected with insulin for 14d. NE turnover in insulin-treated animals given free access to lab chow and a 10% sucrose solution was compared with that obtained in rats fed chow alone or chow plus sucrose. Sucrose ingestion increased NE turnover in heart, brown adipose tissue, and liver, but exogenous insulin did not augment turnover beyond that seen in animals given sucrose alone. This study, therefore, provides no evidence that chronic hyperinsulinemia, sufficient to induce peripheral insulin resistance, stimulates sympathetic activity more than that produced by chronic sucrose ingestion

Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

Science.gov (United States)

Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

2001-12-01

Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

The Sympathetic Release Test: A Test Used to Assess Thermoregulation and Autonomic Control of Blood Flow

Science.gov (United States)

Tansey, E. A.; Roe, S. M.; Johnson, C. J.

2014-01-01

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the…

Adolescent sympathetic activity and salivary C-reactive protein: The effects of parental behavior.

Science.gov (United States)

Nelson, Benjamin W; Byrne, Michelle L; Simmons, Julian G; Whittle, Sarah; Schwartz, Orli S; Reynolds, Eric C; O'Brien-Simpson, Neil M; Sheeber, Lisa; Allen, Nicholas B

2017-10-01

This study utilized a novel multisystem approach to investigate the effect of observed parental behavior on the relationship between biological mechanisms associated with disease processes (i.e., autonomic physiology and immune response) among their adolescent children. Thirty-three adolescents (23 males), aged 11-13, and their parents participated in a laboratory session in which adolescents provided baseline measures of autonomic (sympathetic) activity, and adolescents and 1 parent participated in a laboratory based dyadic conflict resolution interaction task. This included 3 male parent/male adolescent dyads, 20 female parent/male adolescent dyads, 3 male parent/female adolescent dyads, and 7 female parent/female adolescent dyads. Approximately 3 years later, adolescents provided a salivary measure of C-Reactive Protein (sCRP) to index inflammation. Analyses revealed a positive association between sympathetic activity and sCRP, as well as a moderating role of positive parental behavior in this relationship, such that the association between sympathetic activity and sCRP was greater among adolescents whose parents displayed shorter duration of positive affect. Overall findings indicate parental behavior may influence the association between adolescent sympathetic activity and inflammatory processes. These findings have important implications for understanding the impact of psychosocial factors on biological mechanisms of disease. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Relationship between sympathetic activity and response to treatment with atenolol in hypertensive patients. Investigation group of the study of efficiency and tolerance of atenolol in hypertensive patients with increase in the sympathetic activity].

Science.gov (United States)

de la Sierra, A

1999-06-19

Therapeutical response to antihypertensive treatment is poorly predicted by individual clinical or biochemical characteristics. Some preliminary data indicate that therapeutical response to atenolol might depend on physical and/or sympathetic activity. The aim of the present study was to evaluate the blood pressure response to atenolol depending on physical and sympathetic activity. One thousand one hundred forty hypertensive patients were treated with the beta adrenorecepetor blocker atenolol in an open fashion during 3 months. Before the beginning of the treatment, we evaluated current weekly physical activity (direct interview), as well as sympathetic activity (direct interview and baseline heart rate). Age or physical activity did not correlate with blood pressure response to atenolol. Conversely, hypertensive patients with symptoms suggesting sympathetic overactivity (three or more of the following symptoms: palpitations, anxiety, diaphoresis, headache, tremor or weakness; n = 456), showed a more pronounced decrease in systolic (27.7 [13.4] vs 25.8 [14.3] mmHg; p = 0.0226) and diastolic (17.6 [8.3] vs 15.5 [8.6] mmHg; p = 0.0001) blood pressures (SBP and DBP), with respect to the remaining hypertensive patients (n = 719). Moreover, we found a statistically significant correlation between blood pressure fall with atenolol and baseline heart rate (r = 0.107, P anxiety, emotional tension or sympathetic overactivity are associated with a more pronounced blood pressure fall to antihypertensive treatment with atenolol. These circumstances may play a role when choosing a new antihypertensive therapy.

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

Science.gov (United States)

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

International Nuclear Information System (INIS)

Kirby, M.; Stewart, D.

1984-01-01

Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

International Nuclear Information System (INIS)

Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko; Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Nakata, Tomoaki

2014-01-01

Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. 123 I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

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Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

2016-04-01

To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

[Increased sympathetic activity assessed by spectral analysis of heart rate variability in patients with CRPS I].

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Schulze, J; Troeger, C

2010-02-01

The complex regional pain syndrome type I (CRPS I) is a painful neuropathic disorder with an antecedent disproportionate trauma leading to spontaneous pain, hyperalgesia, impaired motor function, swelling, changes in sweating and vascular abnormalities without nerve injury. Whether this syndrome is the result of central or peripheral autonomic dysfunction is still a matter of debate. The purpose of this study was to determine the activity of the sympathetic nervous system in patients with CRPS I by power spectral analysis of heart rate variability. This is a pilot study on 6 patients (mean age 50 years; 4 female, 2 male) diagnosed as suffering from CRPS I and 6 age-matched healthy controls. In the pain-free interval and after taking rest for 5 min, 512 subsequent heart beats were obtained with an ECG standard lead II in the supine and then sitting position. Using an autoregressive model, power spectral densities were calculated for the following frequency bands: CRPS I compared to the healthy controls in the supine position (LF/HF=4.01 vs. LF/HF=1.27; p=0.041). The application of stress by changing to the sitting position even increased that difference (6.72 vs. 1.93). Our results support the hypothesis that the pathogenesis of the early stage CRPS I might be related to an increased sympathetic activity. By assessing the autonomic influence on the heart rate variability in CRPS I patients we could also conclude that this disturbance occurs rather at a central level. Georg Thieme Verlag KG Stuttgart, New York.

Nerve supply to the internal anal sphincter differs from that to the distal rectum: an immunohistochemical study of cadavers.

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Kinugasa, Yusuke; Arakawa, Takashi; Murakami, Gen; Fujimiya, Mineko; Sugihara, Kenichi

2014-04-01

Fecal incontinence is a common problem after anal sphincter-preserving operations. The intersphincteric autonomic nerves supplying the internal anal sphincter (IAS) are formed by the union of: (1) nerve fibers from Auerbach's nerve plexus of the most distal part of the rectum and (2) the inferior rectal branches of the pelvic plexus (IRB-PX) running along the conjoint longitudinal muscle coat. The aim of the present study is to identify the detailed morphology of nerves to the IAS. The study comprised histological and immunohistochemical evaluations of paraffin-embedded sections from a large block of anal canal from the preserved 10 cadavers. The IRB-PX came from the superior aspect of the levator ani and ran into the anal canal on the anterolateral side. These nerves contained both sympathetic and parasympathetic fibers, but the sympathetic content was much higher than in nerves from the distal rectum. All intramural ganglion cells in the distal rectum were neuronal nitric oxide synthase-positive and tyrosine hydroxylase-negative and were restricted to above the squamous-columnar epithelial junction. Parasympathetic nerves formed a lattice-like plexus in the circular smooth muscles of the distal rectum, whereas the IAS contained short, longitudinally running sympathetic and parasympathetic nerves, although sympathetic nerves were dominant. The major autonomic nerve input to the IAS seemed not to originate from the distal rectum but from the IRB-PX. Injury to the IRB-PX during surgery seemed to result in loss of innervation to the major part of the IAS.

Changes in the Skin Conductance Monitor as an End Point for Sympathetic Nerve Blocks.

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Gungor, Semih; Rana, Bhumika; Fields, Kara; Bae, James J; Mount, Lauren; Buschiazzo, Valeria; Storm, Hanne

2017-11-01

There is a lack of objective methods for determining the achievement of sympathetic block. This study validates the skin conductance monitor (SCM) as an end point indicator of successful sympathetic blockade as compared with traditional monitors. This interventional study included 13 patients undergoing 25 lumbar sympathetic blocks to compare time to indication of successful blockade between the SCM indices and traditional measures, clinically visible hyperemia, clinically visible engorgement of veins, subjective skin temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography, within a 30-minute observation period. Differences in the SCM indices were studied pre- and postblock to validate the SCM. SCM showed substantially greater odds of indicating achievement of sympathetic block in the next moment (i.e., hazard rate) compared with all traditional measures (clinically visible hyperemia, clinically visible engorgement of veins, subjective temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography; P ≤ 0.011). SCM indicated successful block for all (100%) procedures, while the traditional measures failed to indicate successful blocks in 16-84% of procedures. The SCM indices were significantly higher in preblock compared with postblock measurements (P SCM is a more reliable and rapid response indicator of a successful sympathetic blockade when compared with traditional monitors. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis.

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Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

2015-01-01

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pperitoneal and deep infiltrating endometriosis.

Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis

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Liang, Yanchun; Wang, Wei; Huang, Jiaming; Tan, Hao; Liu, Tianyu; Shang, Chunliang; Liu, Duo; Guo, Luyan; Yao, Shuzhong

2015-01-01

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (Pendometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (Pendometriosis-associated sympathetic nerve of peritoneal endometriosis (pendometriosis of uterosacral ligament (pendometriosis. PMID:26720585

Targeted NGF siRNA delivery attenuates sympathetic nerve sprouting and deteriorates cardiac dysfunction in rats with myocardial infarction.

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Hesheng Hu

Full Text Available Nerve growth factor (NGF is involved in nerve sprouting, hyper-innervation, angiogenesis, anti-apoptosis, and preservation of cardiac function after myocardial infarction (MI. Positively modulating NGF expression may represent a novel pharmacological strategy to improve post-infarction prognosis. In this study, lentivirus encoding NGF short interfering RNA (siRNA was prepared, and MI was modeled in the rat using left anterior descending coronary artery ligation. Rats were randomly grouped to receive intramyocardial injection of lentiviral solution containing NGF-siRNA (n = 19, MI-SiNGF group, lentiviral solution containing empty vector (n = 18, MI-GFP group or 0.9% NaCl solution (n = 18, MI-control group, or to receive thoracotomy and pericardiotomy (n = 17, sham-operated group. At 1, 2, 4, and 8 wk after transduction, rats in the MI-control group had higher levels of NGF mRNA and protein than those in the sham-operated group, rats in the MI-GFP group showed similar levels as the MI-control group, and rats in the MI-SiNGF group had lower levels compared to the MI-GFP group, indicating that MI model was successfully established and NGF siRNA effectively inhibited the expression of NGF. At 8 wk, echocardiographic and hemodynamic studies revealed a more severe cardiac dysfunction in the MI-siRNA group compared to the MI-GFP group. Moreover, rats in the MI-siRNA group had lower mRNA and protein expression levels of tyrosine hydroxylase (TH and growth-associated protein 43-positive nerve fibers (GAP-43 at both the infarcted border and within the non-infarcted left ventricles (LV. NGF silencing also reduced the vascular endothelial growth factor (VEGF expression and decreased the arteriolar and capillary densities at the infarcted border compared to the MI-GFP group. Histological analysis indicated a large infarcted size in the MI-SiNGF group. These findings suggested that endogenous NGF silencing attenuated sympathetic nerve sprouting

Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

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Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second (Cardiology) Department of Internal Medicine, Sapporo, Hokkaido (Japan)

2014-09-15

Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. {sup 123}I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation.

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Imnadze, Guram; Balzer, Stefan; Meyer, Baerbel; Neumann, Joerg; Krech, Rainer Horst; Thale, Joachim; Franz, Norbert; Warnecke, Henning; Awad, Khaled; Hayek, Salim S; Devireddy, Chandan

2016-12-01

Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter 4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the

Sympathetic ingrowth: A result of cholinergic nerve injury in the adult mammalian brain

International Nuclear Information System (INIS)

Davis, J.N.

1986-01-01

This paper describes sympathetic ingrowth, its regulation and function. The study leads to a better understanding of the molecular mechanisms that probably underlie the regulation of other neuronal rearrangements. The authors examine tritium-2-deoxyglucose uptake in the hippocampal formation after septal leasions. Preliminary experiments suggest that the septo-hippocampal fibers do influence tritium-2-deoxyglucose uptake throughout the hippocampal formation in normal animals. If sympathetic ingrowth also can influence this uptake, this could provide further evidence for an adaptive role of this noradrenergic replacement of cholinergic neurons

Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

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Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M.

1990-01-01

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart

Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

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Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

2015-01-01

Abstract Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32–36 weeks) pregnancy, and post-partum (6–10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min−1 and 16 ± 5 vs. 30 ± 3 bursts min−1 in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min−1 at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal–adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy. Key points Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine

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Wei Chen

Full Text Available Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2, angiotensin (Ang-(1-7 and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial pressure (MAP were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7 and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Inhibition of facilitation of sympathetic neurotransmission and angiotensin II-induced pressor effects in the pithed rat: comparison between valsartan, candesartan, eprosartan and embusartan

NARCIS (Netherlands)

Balt, J. C.; Mathy, M. J.; Pfaffendorf, M.; van Zwieten, P. A.

2001-01-01

In the pithed rat model, endogenously generated angiotensin (Ang) II can enhance sympathetic neurotransmission by acting on Ang II type 1 (AT1) receptors that are located on sympathetic nerve terminals. To compare the inhibitory potency of candesartan, valsartan, eprosartan and embusartan in

Sympathetically maintained pain presenting first as temporomandibular disorder, then as parotid dysfunction.

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Giri, Subha; Nixdorf, Donald

2007-03-01

Complex regional pain syndrome (CRPS) is a chronic condition characterized by intense pain, swelling, redness, hypersensitivity and additional sudomotor effects. In all 13 cases of CRPS in the head and neck region reported in the literature, nerve injury was identified as the etiology for pain initiation. In this article, we present the case of a 30-year-old female patient with sympathetically maintained pain without apparent nerve injury. Her main symptoms--left-side preauricular pain and inability to open her mouth wide--mimicked temporomandibular joint arthralgia and myofascial pain of the masticatory muscles. Later, symptoms of intermittent preauricular pain and swelling developed, along with hyposalivation, which mimicked parotitis. After an extensive diagnostic process, no definitive underlying pathology could be identified and a diagnosis of neuropathic pain with a prominent sympathetic component was made. Two years after the onset of symptoms and initiation of care, treatment with repeated stellate ganglion blocks and enteral clonidine pharmacotherapy provided adequate pain relief.

Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

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Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

2018-05-22

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface

Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

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Dianne Lorton

2015-03-01

Full Text Available Cross-talk between the sympathetic nervous system (SNS and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs in immune cells activates the cAMP-protein kinase A (PKA intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells.

Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

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Kamiya, Atsunori; Michikami, Daisaku; Shiozawa, Tomoki; Iwase, Satoshi; Hayano, Junichiro; Kawada, Toru; Sunagawa, Kenji; Mano, Tadaaki

2004-05-01

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P antigravity leg muscles.

Origins of the sympathetic innervation to the nasal-associated lymphoid tissue (NALT): an anatomical substrate for a neuroimmune connection.

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Marafetti, Lucas E; Romeo, Horacio E

2014-11-15

The participation of sympathetic nerve fibers in the innervation of the nasal-associated lymphoid tissues (NALT) was investigated in hamsters. Vesicular monoamine transporter 2 (VMAT2), an established sympathetic marker, is expressed in all neurons of superior cervical ganglia (SCG). In addition, VMAT2 -immunoreactive nerve fibers were localized in the NALT as well as in adjacent anatomical structures of the upper respiratory tract. Unilateral surgical ablation of the SCG abolished VMAT2 innervation patterns ipsilaterally while the contra lateral side is unaffected. These results provide the anatomical substrate for a neuroimmune connection in the NALT. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative assessment of integrated phrenic nerve activity.

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Nichols, Nicole L; Mitchell, Gordon S

2016-06-01

Integrated electrical activity in the phrenic nerve is commonly used to assess within-animal changes in phrenic motor output. Because of concerns regarding the consistency of nerve recordings, activity is most often expressed as a percent change from baseline values. However, absolute values of nerve activity are necessary to assess the impact of neural injury or disease on phrenic motor output. To date, no systematic evaluations of the repeatability/reliability have been made among animals when phrenic recordings are performed by an experienced investigator using standardized methods. We performed a meta-analysis of studies reporting integrated phrenic nerve activity in many rat groups by the same experienced investigator; comparisons were made during baseline and maximal chemoreceptor stimulation in 14 wild-type Harlan and 14 Taconic Sprague Dawley groups, and in 3 pre-symptomatic and 11 end-stage SOD1(G93A) Taconic rat groups (an ALS model). Meta-analysis results indicate: (1) consistent measurements of integrated phrenic activity in each sub-strain of wild-type rats; (2) with bilateral nerve recordings, left-to-right integrated phrenic activity ratios are ∼1.0; and (3) consistently reduced activity in end-stage SOD1(G93A) rats. Thus, with appropriate precautions, integrated phrenic nerve activity enables robust, quantitative comparisons among nerves or experimental groups, including differences caused by neuromuscular disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Localization and neurochemical characteristics of the extrinsic sympathetic neurons projecting to the pylorus in the domestic pig.

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Zalecki, Michal

2012-01-01

The pylorus, an important part of the digestive tract controlling the flow of chyme between the stomach and the duodenum, is widely innervated by intrinsic and extrinsic nerves. To determine the locations of postganglionic sympathetic perikarya that innervate the pylorus of the domestic pig, a retrograde tracing method with application of Fast Blue tracer was used. All positive neuronal cell bodies (ca. 1750) were found in the celiac-cranial mesenteric ganglion complex (CSMG), however, the coeliac poles of this complex provided the major input to the pylorus. Afterwards, the immunohistochemical staining procedure was applied to determine biologically active substances expressed in the FB-labeled perikarya. Approximately 77% of the FB-positive cell bodies contained tyrosine hydroxylase (TH), 87% dopamine β-hydroxylase (DβH), 40% neuropeptide Y (NPY), 12% somatostatin (SOM) and 7% galanin (GAL). The presence of all these substances in the ganglion tissue was confirmed by RT-PCR technique. Double immunocytochemistry revealed that all of the TH-positive perikarya contained DβH, about 40% NPY, 12% SOM and 8% GAL. Additionally, all above-cited immunohistochemical markers as well as VIP, PACAP, ChAT, LEU, MET, SP and nNOS were observed within nerve fibers associated with the FB-positive perikarya. Immunocytochemical labeling of the pyloric wall tissue disclosed that TH+, DβH+ and NPY+ nerve fibers innervated ganglia of the myenteric and submucosal plexuses, blood vessels, both muscular layers and the muscularis mucosae; nerve fibers immunoreactive to GAL mostly innervated both muscular layers, while SOM+ nerve fibers were observed within the myenteric plexus. Presented study revealed sources of origin and immunohistochemical characteristics of the sympathetic postganglionic perikarya innervating the porcine pylorus. Copyright © 2011 Elsevier B.V. All rights reserved.

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy

International Nuclear Information System (INIS)

Momose, Mitsuru; Inaba, Shigeki; Emori, Toshiaki; Imamura, Kimiharu; Kawano, Katsunori; Ueda, Tetsuro; Kobayashi, Hideki; Hosoda, Saichi

1997-01-01

Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity. (orig.). With 4 figs., 2 tabs

Artifacts produced during electrical stimulation of the vestibular nerve in cats. [autonomic nervous system components of motion sickness

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Tang, P. C.

1973-01-01

Evidence is presented to indicate that evoked potentials in the recurrent laryngeal, the cervical sympathetic, and the phrenic nerve, commonly reported as being elicited by vestibular nerve stimulation, may be due to stimulation of structures other than the vestibular nerve. Experiments carried out in decerebrated cats indicated that stimulation of the petrous bone and not that of the vestibular nerve is responsible for the genesis of evoked potentials in the recurrent laryngeal and the cervical sympathetic nerves. The phrenic response to electrical stimulation applied through bipolar straight electrodes appears to be the result of stimulation of the facial nerve in the facial canal by current spread along the petrous bone, since stimulation of the suspended facial nerve evoked potentials only in the phrenic nerve and not in the recurrent laryngeal nerve. These findings indicate that autonomic components of motion sickness represent the secondary reactions and not the primary responses to vestibular stimulation.

Anatomy of the nerves and ganglia of the aortic plexus in males

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Beveridge, Tyler S; Johnson, Marjorie; Power, Adam; Power, Nicholas E; Allman, Brian L

2015-01-01

It is well accepted that the aortic plexus is a network of pre- and post-ganglionic nerves overlying the abdominal aorta, which is primarily involved with the sympathetic innervation to the mesenteric, pelvic and urogenital organs. Because a comprehensive anatomical description of the aortic plexus and its connections with adjacent plexuses are lacking, these delicate structures are prone to unintended damage during abdominal surgeries. Through dissection of fresh, frozen human cadavers (n = 7), the present study aimed to provide the first complete mapping of the nerves and ganglia of the aortic plexus in males. Using standard histochemical procedures, ganglia of the aortic plexus were verified through microscopic analysis using haematoxylin & eosin (H&E) and anti-tyrosine hydroxylase stains. All specimens exhibited four distinct sympathetic ganglia within the aortic plexus: the right and left spermatic ganglia, the inferior mesenteric ganglion and one previously unidentified ganglion, which has been named the prehypogastric ganglion by the authors. The spermatic ganglia were consistently supplied by the L1 lumbar splanchnic nerves and the inferior mesenteric ganglion and the newly characterized prehypogastric ganglion were supplied by the left and right L2 lumbar splanchnic nerves, respectively. Additionally, our examination revealed the aortic plexus does have potential for variation, primarily in the possibility of exhibiting accessory splanchnic nerves. Clinically, our results could have significant implications for preserving fertility in men as well as sympathetic function to the hindgut and pelvis during retroperitoneal surgeries. PMID:25382240

Separate neurochemical classes of sympathetic postganglionic neurons project to the left ventricle of the rat heart.

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Richardson, R J; Grkovic, I; Allen, A M; Anderson, C R

2006-04-01

The sympathetic innervation of the rat heart was investigated by retrograde neuronal tracing and multiple label immunohistochemistry. Injections of Fast Blue made into the left ventricular wall labelled sympathetic neurons that were located along the medial border of both the left and right stellate ganglia. Cardiac projecting sympathetic postganglionic neurons could be grouped into one of four neurochemical populations, characterised by their content of calbindin and/or neuropeptide Y (NPY). The subpopulations of neurons contained immunoreactivity to both calbindin and NPY, immunoreactivity to calbindin only, immunoreactivity to NPY only and no immunoreactivity to calbindin or NPY. Sympathetic postganglionic neurons were also labelled in vitro with rhodamine dextran applied to the cut end of a cardiac nerve. The same neurochemical subpopulations of sympathetic neurons were identified by using this technique but in different proportions to those labelled from the left ventricle. Preganglionic terminals that were immunoreactive for another calcium-binding protein, calretinin, preferentially surrounded retrogradely labelled neurons that were immunoreactive for both calbindin and NPY. The separate sympathetic pathways projecting to the rat heart may control different cardiac functions.

Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol on parasympathetic and sympathetic activity: a comparison of clinical results

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Heather L. Bloom

2014-08-01

Full Text Available Background Cardiovascular autonomic neuropathy (CAN is recognized as a significant health risk, correlating with risk of heart disease, silent myocardial ischemia or sudden cardiac death. Beta-blockers are often prescribed to minimize risk. Objectives In this second of two articles, the effects on parasympathetic and sympathetic activity of the alpha/beta-adrenergic blocker, Carvedilol, are compared with those of the selective beta-adrenergic blocker, Metoprolol. Methods Retrospective, serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1 introduced, (2 discontinued or (3 continued without adjustment. Group 3 served as the control. Results Introducing Carvedilol or Metoprolol decreased heart rate and blood pressure, and discontinuing them had the opposite effect. Parasympathetic activity increased with introducing Carvedilol. Sympathetic activity increased more after discontinuing Carvedilol, suggesting better sympathetic suppression. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. Conclusion Carvedilol has a more profound effect on sympathovagal balance than Metoprolol. While both suppress sympathetic activity, only Carvedilol increases parasympathetic activity. Increased parasympathetic activity may underlie the lower mortality risk with Carvedilol.

Temporary Blindness after Inferior Alveolar Nerve Block.

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Barodiya, Animesh; Thukral, Rishi; Agrawal, Shaila Mahendra; Rai, Anshul; Singh, Siddharth

2017-03-01

Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures in dental clinic. This procedure is safe, but complications may still occur. Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are extremely rare. This case report explains an event where due to individual anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and middle meningeal arteries, intravascular administration of anaesthetic agent caused unusual ocular signs and symptoms such as temporary blindness.

BLOCKADE OF ROSTRAL VENTROLATERAL MEDULLA (RVLM BOMBESIN RECEPTOR TYPE 1 DECREASES BLOOD PRESSURE AND SYMPATHETIC ACTIVITY IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

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Izabella Silva De Jesus Pinto

2016-06-01

Full Text Available IIntrathecal injection of bombesin (BBS promoted hypertensive and sympathoexcitatory effects in normotensive (NT rats. However, the involvement of rostral ventrolateral medulla (RVLM in these responses is still unclear. In the present study, we investigated: (1 the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR; (2 the contribution of RVLM bombesin type 1 receptors (BB1 to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v. were instrumented to record mean arterial pressure (MAP, diaphragm (DIA motor and renal sympathetic nerve activity (RSNA. In NT rats and SHR, BBS (0.3 mM nanoinjected into RVLM increased MAP (33.9 ± 6.6 mmHg and 37.1 ± 4.5 mmHg, respectively; p < 0.05 and RSNA (97.8 ± 12.9 % and 84.5 ± 18.1 %, respectively; p < 0.05. In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7 %; p < 0.05. BB1 receptors antagonist (BIM-23127; 3 mM reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05 and RSNA (-17.7 ± 3.8 %; p < 0.05 in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6 %, respectively. These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

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Nomura, Yusuke; Kajinami, Kouji; Matsunari, Ichiro; Takamatsu, Hiroyuki; Murakami, Yoshihiro; Matsuya, Takahiro; Chen, Wei-Ping; Taki, Junichi; Nakajima, Kenichi; Nekolla, Stephan G.

2006-01-01

Although 11 C-hydroxyephedrine ( 11 C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of 11 C-HED PET in small- to medium-sized animals. Furthermore, its relation to 123 I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using 11 C-HED PET, and to compare the retention of 11 C-HED with that of 123 I-MIBG. Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of 11 C-HED and 123 I-MIBG, all animals underwent dynamic 11 C-HED PET for 40 min with arterial blood sampling. The 11 C-HED retention fraction and normalised 11 C-HED activity measured by tissue sampling were compared with those measured by PET. Both the 11 C-HED retention fraction and the normalised 11 C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p 11 C-HED and 123 I-MIBG. Reserpine pretreatment reduced 11 C-HED retention by 50%, but did not reduce 123 I-MIBG retention at 40 min after injection. Non-invasive quantitation of cardiac sympathetic innervation using 11 C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both 11 C-HED and 123 I-MIBG are specific for sympathetic neurons, 11 C-HED may be more specific for intravesicular uptake than 123 I-MIBG in some situations, such as that seen in reserpine pretreatment. (orig.)

Neural and sympathetic activity associated with exploration in decision-making: Further evidence for involvement of insula

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Hideki eOhira

2014-11-01

Full Text Available We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition and a condition with high uncertainty of gain/loss (random-reward condition. Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET, and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.

Enhanced sympathetic arousal in response to FMRI scanning correlates with task induced activations and deactivations.

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Markus Muehlhan

Full Text Available It has been repeatedly shown that functional magnetic resonance imaging (fMRI triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA, as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults.

Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

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Lin Li

Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

Effects of 12 months continuous positive airway pressure on sympathetic activity related brainstem function and structure in obstructive sleep apnea.

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Luke Anthony Henderson

2016-03-01

Full Text Available Muscle sympathetic nerve activity (MSNA is greatly elevated in patients with obstructive sleep apnoea (OSA during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 subjects with OSA prior to and following 6 and 12 months of continuous positive airway pressure (CPAP treatment. We found that 6 and 12 months of CPAP treatment significantly reduced the elevated resting MSNA in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MNSA likely due to its effects on restoring brainstem structure and function.

Nerve-muscle activation by rotating permanent magnet configurations.

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Watterson, Peter A; Nicholson, Graham M

2016-04-01

The standard method of magnetic nerve activation using pulses of high current in coils has drawbacks of high cost, high electrical power (of order 1 kW), and limited repetition rate without liquid cooling. Here we report a new technique for nerve activation using high speed rotation of permanent magnet configurations, generating a sustained sinusoidal electric field using very low power (of order 10 W). A high ratio of the electric field gradient divided by frequency is shown to be the key indicator for nerve activation at high frequencies. Activation of the cane toad sciatic nerve and attached gastrocnemius muscle was observed at frequencies as low as 180 Hz for activation of the muscle directly and 230 Hz for curved nerves, but probably not in straight sections of nerve. These results, employing the first prototype device, suggest the opportunity for a new class of small low-cost magnetic nerve and/or muscle stimulators. Conventional pulsed current systems for magnetic neurostimulation are large and expensive and have limited repetition rate because of overheating. Here we report a new technique for nerve activation, namely high-speed rotation of a configuration of permanent magnets. Analytical solutions of the cable equation are derived for the oscillating electric field generated, which has amplitude proportional to the rotation speed. The prototype device built comprised a configuration of two cylindrical magnets with antiparallel magnetisations, made to rotate by interaction between the magnets' own magnetic field and three-phase currents in coils mounted on one side of the device. The electric field in a rectangular bath placed on top of the device was both numerically evaluated and measured. The ratio of the electric field gradient on frequency was approximately 1 V m(-2) Hz(-1) near the device. An exploratory series of physiological tests was conducted on the sciatic nerve and attached gastrocnemius muscle of the cane toad (Bufo marinus). Activation was

Revision on Renal Sympathetic Ablation in the Treatment of Resistant Hypertension.

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Saraiva, Ana Filipa

2016-01-01

Hypertension is one of the most prevalent diseases in the world, with about 1 billion people affected and a possible increase to 1.5 billion by 2025. Despite advances in treatment, a proportion of patients remain resistant to conventional treatment and uncontrolled, and this can adversely affect future cardiovascular events and mortality. This alarming growth is already reflected in an important public health problem and one of the largest economic burdens of health, requiring new approaches and development of different strategies to fight this problem. This review will focus on the definition of resistant hypertension and its etiology, as well as in contemporary evidence supporting the usefulness of renal sympathetic denervation while addressing current and emerging devices, potential treatment indications in the future and unresolved issues that need to be addressed before renal sympathetic denervation can be adopted not only as a last resort exclusively for resistant hypertension. Finally an evaluation algorithm for patients with resistant hypertension which should be implemented before the execution of this technique will be proposed. Renal sympathetic denervation is a technique that possibly could have future implications in the population with hypertension, especially those with true resistant hypertension. This technique aims to reduce the renal sympathetic activation (a component in the pathophysiology of hypertension) through the destruction of the renal sympathetic nerves located in the adventitia of the renal arteries. There are several catheters that can be used; each with its specifications and therefore their selection should be made individually depending on the profile of the patient. However, a detailed pre-procedure evaluation is extremely important to exclude the large percentage of individuals with uncontrolled hypertension due to several factors that make it impossible to control blood pressure, but are likely to be corrected and as such should

Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords

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Chun-Kuei Su

2018-03-01

Full Text Available Nitric oxide (NO is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM. NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors, indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker, gabazine (a GABAA receptor blocker, or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor

[Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

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Indo, Yasuhiro

2015-05-01

Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

Glutamate and GABA in vestibulo-sympathetic pathway neurons

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Gay R Holstein

2016-02-01

Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

Mean 24-hours sympathetic nervous system activity decreases during head-down tilted bed rest but not during microgravity

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Christensen, Nj; Heer, M.; Ivanova, K.; Norsk, P.

Sympathetic nervous system activity is closely related to gravitational stress in ground based experiments. Thus a high activity is present in the standing-up position and a very low activity is observed during acute head-out water immersion. Adjustments in sympathetic activity are necessary to maintain a constant blood pressure during variations in venous return. Head-down tilted bed rest is applied as a model to simulate changes observed during microgravity. The aim of the present study was to test the hypothesis that mean 24-hours sympathetic activity was low and similar during space flight and in ground based observation obtained during long-term head-down tilted bed rest. Forearm venous plasma noradrenaline was measured by a radioenzymatic technique as an index of muscle sympathetic activity and thrombocyte noradrenaline and adrenaline were measured as indices of mean 24-hours sympathoadrenal activity. Previous results have indicated that thrombocyte noradrenaline level has a half-time of 2 days. Thus to reflect sympathetic activity during a specific experiment the study period must last for at least 6 days and a sample must be obtained within 12 hours after the experiment has ended. Ten normal healthy subjects were studied before and during a 14 days head-down tilted bed rest as well as during an ambulatory study period of a similar length. The whole experiment was repeated while the subjects were on a low calorie diet. Thrombocyte noradrenaline levels were studied in 4 cosmonauts before and within 12 hours after landing after more than 7 days in flight. Thrombocyte noradrenaline decreased markedly during the head-down tilted bed rest (pdifferent in cosmonauts and in subjects participating in the head down tilted bed rest study (170± 29% (Mean± SEM) vs. 57± 7%, respectively; presponse to combined effects of a reduced plasma volume and an increased vascular capacity in flight.

Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

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Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

2015-04-01

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

Unusually large quiescent ancient schwannoma of hypoglossal nerve

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Sangeeta P Wanjari

2013-01-01

Full Text Available Ancient schwannoma is considered as a variant of schwannoma, comprising about 10% of all schwanommas. Schwannoma is a benign neoplasm derived from the nerve sheath of peripheral motor, sensory and sympathetic nerves and from the cranial nerve pairs. It usually presents as a solitary soft-tissue lesion which is slow growing, encapsulated and is often associated with nerve attached peripherally. Diagnosis is often confirmed with the microscopic examination. The long standing schwannoma attributes to degenerative changes and is termed "ancient" schwannoma. Present case is of a 68-year-old female patient who reported with an asymptomatic large swelling below mandible on the left side since last 23 years. The lesion was surgically excised under general anesthesia.

Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice

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Campbell, J. Preston; Karolak, Matthew R.; Ma, Yun; Perrien, Daniel S.; Masood-Campbell, S. Kathryn; Penner, Niki L.; Munoz, Steve A.; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A.; Elefteriou, Florent

2012-01-01

Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depr...

The renal nerves in chronic heart failure: efferent and afferent mechanisms

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Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

The Renal Nerves in Chronic Heart Failure: Afferent and Efferent Mechanisms

Directory of Open Access Journals (Sweden)

Alicia Marie Schiller

2015-08-01

Full Text Available The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF. Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent

Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

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Marcus May

Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

Science.gov (United States)

May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

2011-01-01

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

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Jihong Xing

2016-11-01

Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

The gross anatomy of the renal sympathetic nerves revisited.

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Mompeo, Blanca; Maranillo, Eva; Garcia-Touchard, Arturo; Larkin, Theresa; Sanudo, Jose

2016-07-01

Catheter-based renal denervation techniques focus on reducing blood pressure in resistant hypertension. This procedure requires exact knowledge of the anatomical interrelation between the renal arteries and the targeted renal nervous plexus. The aim of this work was to build on classical anatomical studies and describe the gross anatomy and anatomical relationships of the renal arteries and nerve supply to the kidneys in a sample of human cadavers. Twelve human cadavers (six males and six females), age range 73 to 94 years, were dissected. The nervous fibers and renal arteries were dissected using a surgical microscope. The renal plexus along the hilar renal artery comprised a fiber-ganglionic ring surrounding the proximal third of the renal artery, a neural network along the middle and distal thirds, and smaller accessory ganglia along the course of the nerve fibers. The fibers of the neural network were mainly located on the superior (95.83%) and inferior (91.66%) surfaces of the renal artery and they were sparsely interconnected by diagonal fibers. Polar arteries were present in 33.33% of cases and the renal nerve pattern for these was similar to that of the hilar arteries. Effective renal denervation needs to target the superior and inferior surfaces of the hilar and polar arteries, where the fibers of the neural network are present. Clin. Anat. 29:660-664, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Recovery of colonic transit following extrinsic nerve damage in rats.

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Ridolfi, Timothy J; Tong, Wei Dong; Kosinski, Lauren; Takahashi, Toku; Ludwig, Kirk A

2011-06-01

Injury to pelvic sympathetic and parasympathetic nerves from surgical and obstetrical trauma has long been cited as a cause for abnormal colorectal motility in humans. Using a rat model, acute transaction of these extrinsic nerves has been shown to effect colorectal motility. The aim of this study is to determine in a rat model how transection of these extrinsic nerves affects colonic transit over time. Eighty-two Sprague-Dawley rats underwent placement of a tunneled catheter into the proximal colon. Bilateral hypogastric, pelvic nerves (HGN and PN) or both were transected in 66 rats. The remaining 16 rats received a sham operation. Colonic transit was evaluated at postoperative days (PODs) 1, 3, and 7 by injecting and calculating the geometric center (GC) of the distribution of (51)Cr after 3 h of propagation. At POD 1, transection of PNs significantly delayed colonic transit (GC = 4.9, p < 0.05), while transection of HGNs (GC = 8.5, p < 0.05) or transection of both nerves (GC = 7.8, p < 0.05) significantly accelerated colonic transit, when compared with sham operation (GC = 6.0). A significant trend toward recovery was noted in both the HGN and PN transection groups at POD 7. Damage to the extrinsic sympathetic and/or parasympathetic PNs affects colonic transit acutely. These changes in large bowel motor function normalize over time implicating a compensatory mechanism within the bowel itself.

Novel Approaches for the Treatment of the Patient with Resistant Hypertension: Renal Nerve Ablation

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Gulati, Vinay; White, William B.

2013-01-01

Sympathetic innervation of the kidneys plays a major role in the pathogenesis of hypertension through modulation of renin secretion, glomerular filtration rate and renal absorption of sodium. Targeted interventions for renal nerve ablation are being developed for treatment of drug resistant hypertension in the USA and rest of the world. Early studies with the use of radiofrequency based renal denervation systems have shown encouraging results with significant reduction of blood pressure in patients inadequately controlled despite nearly maximal drug therapy regimens. Thus far, the renal denervation procedure has been associated with minimal side effects. Long term efficacy and safety beyond 3 years needs to be determined for renal nerve ablation. This review focuses on the physiology of the renal sympathetic system, the rationale for renal nerve ablation and current evidence in support of the available therapeutic renal denervation systems. PMID:24244757

Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity

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El-Sheikh, Mona; Kouros, Chrystyna D.; Erath, Stephen; Cummings, E. Mark; Keller, Peggy; Staton, Lori

2009-01-01

Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS) activity were examined as moderators. PNS activity was indexed by respiratory sinus arrhythmia (RSA) and RSA reactivity (RSA-R) to lab…

Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.

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Li, Dan; Lu, Chieh-Ju; Hao, Guoliang; Wright, Hannah; Woodward, Lavinia; Liu, Kun; Vergari, Elisa; Surdo, Nicoletta C; Herring, Neil; Zaccolo, Manuela; Paterson, David J

2015-07-01

Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission. © 2015 American Heart Association, Inc.

The pattern of activation of the sympathetic nervous system during tilt-induced syncope.

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Zyśko, Dorota; Gajek, Jacek; Sciborski, Ryszard; Smereka, Jacek; Checiński, Igor; Mazurek, Walentyna

2007-04-01

A 49-year-old patient with a history of situational syncope and minimal electrocardiographic signs of accessory pathway is described. The evidence for pre-excitation was present only during the sympathetic activation caused by exercise testing and isoprenaline infusion. This phenomenon served as an indicator of significant adrenergic drive to the heart after the tilt-induced syncope. The meaning of the observed electrocardiographic changes in the course of neurocardiogenic reaction and its contribution to the understanding of the sympatho-vagal balance during vasovagal syncope is discussed. The lack of preexcitation signs during syncope and its appearance several seconds after the syncope-related sinus pause indicates sympathetic withdrawal before and shortly after the asystole. The possible pathophysiological mechanisms are discussed.

Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

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Jarvis, Sara S.; VanGundy, Tiffany B.; Galbreath, M. Melyn; Shibata, Shigeki; Okazaki, Kazunobu; Reelick, Miriam F.; Levine, Benjamin D.

2011-01-01

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents. PMID:21508291

Sympathetic reflex control of blood flow in human peripheral tissues

DEFF Research Database (Denmark)

Henriksen, O

1991-01-01

Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

Renal sympathetic denervation for resistant hypertension.

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Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

2013-05-01

Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Experimental study of vascularized nerve graft: evaluation of nerve regeneration using choline acetyltransferase activity.

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Iwai, M; Tamai, S; Yajima, H; Kawanishi, K

2001-01-01

A comparative study of nerve regeneration was performed on vascularized nerve graft (VNG) and free nerve graft (FNG) in Fischer strain rats. A segment of the sciatic nerve with vascular pedicle of the femoral artery and vein was harvested from syngeneic donor rat for the VNG group and the sciatic nerve in the same length without vascular pedicle was harvested for the FNG group. They were transplanted to a nerve defect in the sciatic nerve of syngeneic recipient rats. At 2, 4, 6, 8, 12, 16, and 24 weeks after operation, the sciatic nerves were biopsied and processed for evaluation of choline acetyltransferase (CAT) activity, histological studies, and measurement of wet weight of the muscle innervated by the sciatic nerve. Electrophysiological evaluation of the grafted nerve was also performed before sacrifice. The average CAT activity in the distal to the distal suture site was 383 cpm in VNG and 361 cpm in FNG at 2 weeks; 6,189 cpm in VNG and 2,264 cpm in FNG at 4 weeks; and 11,299 cpm in VNG and 9,424 cpm in FNG at 6 weeks postoperatively. The value of the VNG group was statistically higher than that of the FNG group at 4 weeks postoperatively. Electrophysiological and histological findings also suggested that nerve regeneration in the VNG group was superior to that in the FNG group during the same period. However, there was no significant difference between the two groups after 6 weeks postoperatively in any of the evaluations. The CAT measurement was useful in the experiments, because it was highly sensitive and reproducible. Copyright 2001 Wiley-Liss, Inc.

Microanatomical and immunohistochemical study of the human lateral antebrachial cutaneous nerve of forearm at the antecubital fossa and its clinical implications.

Science.gov (United States)

Marx, S Chakravarthy; Kumar, Pramod; Dhalapathy, S; Prasad, Keerthana; Marx, C Anitha

2010-09-01

Changes in the intraneural anatomy with age can cause poor prognosis of nerve repair in patients after nerve injury. The occurrence of Complex Regional Pain Syndrome-Type II, secondary to peripheral nerve injury, is common. The purpose of this study is to asses changes in cross-sectional anatomy of the lateral antebrachial cutaneous nerve of forearm (LCNF) at the antecubital fossa in the fascicular, nonfascicular components (adipose and nonadipose tissue), and sympathetic fibers area with respect to age. For the purpose of the study, 32 human (37-88 years) fresh cadaveric LCNF were collected from left-antecubital fossae and processed for histological, morphometric analysis [total cross-sectional (Asc), fascicular (Af), and nonfascicular area (Anonf)], and immunohistochemical method (tyrosine hydroxylase) for sympathetic fibers. The LCNF's average total cross-sectional area was 3.024 mm(2), and fascicular area was 0.582 mm(2). The average number of fascicles per mm(2) was 3.09. The cross-sectional area in the nerve was mainly occupied by nonfascicular connective tissue (80.75%). There was increased adipose tissue deposition (48.48% of Asc) and decreased collagen fibers (32.24% of Asc) in interfascicular domains without any definite relationship with age. The average sympathetic fiber area was 0.026 mm(2) within the nerve fascicular area without any correlation with age. In LCNF, there was more adipose tissue and less collagen fibers deposition in the interfascicular domains of all age cases, and this may act as an obstacle for nerve fiber regeneration on using LCNF as an interpositional nerve graft.

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs?

Directory of Open Access Journals (Sweden)

Denise L. Bellinger

2018-04-01

Full Text Available Immune-Mediated Inflammatory Diseases (IMIDs is a descriptive term coined for an eclectic group of diseases or conditions that share common inflammatory pathways, and for which there is no definitive etiology. IMIDs affect the elderly most severely, with many older individuals having two or more IMIDs. These diseases include, but are not limited to, type-1 diabetes, obesity, hypertension, chronic pulmonary disease, coronary heart disease, inflammatory bowel disease, and autoimmunity, such as rheumatoid arthritis (RA, Sjőgren’s syndrome, systemic lupus erythematosus, psoriasis, psoriatic arthritis, and multiple sclerosis. These diseases are ostensibly unrelated mechanistically, but increase in frequency with age and share chronic systemic inflammation, implicating major roles for the spleen. Chronic systemic and regional inflammation underlies the disease manifestations of IMIDs. Regional inflammation and immune dysfunction promotes targeted end organ tissue damage, whereas systemic inflammation increases morbidity and mortality by affecting multiple organ systems. Chronic inflammation and skewed dysregulated cell-mediated immune responses drive many of these age-related medical disorders. IMIDs are commonly autoimmune-mediated or suspected to be autoimmune diseases. Another shared feature is dysregulation of the autonomic nervous system and hypothalamic pituitary adrenal (HPA axis. Here, we focus on dysautonomia. In many IMIDs, dysautonomia manifests as an imbalance in activity/reactivity of the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS. These major autonomic pathways are essential for allostasis of the immune system, and regulating inflammatory processes and innate and adaptive immunity. Pathology in ANS is a hallmark and causal feature of all IMIDs. Chronic systemic inflammation comorbid with stress pathway dysregulation implicate neural-immune cross-talk in the etiology and pathophysiology of IMIDs

Polyphenols, Antioxidants and the Sympathetic Nervous System.

Science.gov (United States)

Bruno, Rosa Maria; Ghiadoni, Lorenzo

2018-01-01

A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic

Distribution of lymphatic tissues and autonomic nerves in supporting ligaments around the cervix uteri.

Science.gov (United States)

Zhang, Jianping; Feng, Lanlan; Lu, Yi; Guo, Dongxia; Xi, Tengteng; Wang, Xiaochun

2013-05-01

To investigate the distribution of lymphatic tissues and nerves in the supporting ligaments around the cervix uteri for their tomographical relationship, 9 adult female cadavers were used in this study. Following the incision of all supporting ligaments around the cervix, hematoxylin and esosin (H&E) and immunohistochemical staining of various sections of these ligaments was performed to enable the distribution of lymph tissues and autonomic nerves to be observed. Four lymph nodes were identified in three cadaver specimens. Three lymph nodes were present at a distance of 2.0 cm from the cervix in the cranial side of the cardinal ligaments (CLs), and one lymph node was located at a distance of 4.0 cm from the cervix in the cranial side of the uterosacral ligament (USL). The lymphatic vessels were dispersed in the CLs, scattered in the cervical side of the USLs, and occasionally distributed in the vesicouterine ligaments (VULs). In the CLs, parasympathetic nerves were located at the pelvic lateral wall and went downwards and medially into the cervix, while sympathetic fibers were located in the middle and lower parts of the ligaments. In the USLs, the autonomic nerves, which consisted primarily of sympathetic fibers, went downwards and laterally from the pelvic wall to the cervix. In the VULs, parasympathetic and sympathetic nerves were located in the inner sides of the vesical veins in the deep layers of the ligaments. It is concluded that there are few lymphatic tissues in the supporting ligaments around the cervix uteri, and that nerve‑sparing radical hysterectomy (NSRH) may be a safe method for the treatment of early‑stage cervical cancer.

Nerve endings in the heart of teleosts.

Science.gov (United States)

Kumar, S

1979-01-01

The nerve endings in the heart of fishes were studied using silver impregnation techniques. The heart chambers are profusely innervated by the sympathetic, parasympathetic (vagal) and postganglionic fibers of the intracardiac ganglia situated at the sinuatrial and the atrioventricular junctions. The plexuses are composed of medullated and nonmedullated fibers. The nerve fibers generally end freely and are slightly branched or unbranched terminations of myelinated and unmyelinated fibers. Moreover, a few nerve fibers end redundant in the form of end-rings, bulb-like, bush-like, club-shaped end end-coil like structures. The complex unencapsulated types of endings are also found in the myocardium of the atrium and the ventricle. The encapsulated endings (Vater-Pacinian; Krause end-bulb) could not be observed.

A microcontroller-based telemetry system for sympathetic nerve activity and ECG measurement.

Science.gov (United States)

Harada, E; Yonezawa, Y; Caldwell, W M; Hahn, A W

1999-01-01

A telemetry system employing a low power 8-bit microcontroller has been developed for chronic unanesthetized small animal studies. The two-channel system is designed for use with animals in shielded cages. Analog signals from implantable ECG and nerve electrodes are converted to an 8-bit serial digital format. This is accomplished by individual 8 bit A/D converters included in the microcontroller, which also has serial I/O port. The converted serial binary code is applied directly to an antenna wire. Therefore, the system does not need to employ a separate transmitter, such as in FM or infrared optical telemeters. The system is used in a shielded animal cage to reduce interference from external radio signals and 60 Hz power line fields. The code is received by a high input impedance amplifier in the cage and is then demodulated. The telemeter is powered by a small 3 V lithium battery, which provides 100 hours of continuous operation. The circuit is constructed on two 25 x 25 mm. printed circuit boards and encapsulated in epoxy, yielding a total volume of 6.25 cc. The weight is 15 g.

Mechanisms of Sympathetic Activation and Blood Pressure Elevation by Intermittent Hypoxia

OpenAIRE

Prabhakar, Nanduri R.; Kumar, Ganesh K.

2010-01-01

Sleep disordered breathing with recurrent apneas is one of the most frequently encountered breathing disorder in adult humans and preterm infants. Recurrent apnea patients exhibit several co-morbidities including hypertension and persistent sympathetic activation. Intermittent hypoxia (IH) resulting from apneas appears to be the primary stimulus for evoking autonomic changes. The purpose of this article is to briefly review the effects of IH on chemo-and baro-reflexes and circulating vasoacti...

Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

Science.gov (United States)

Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

2015-01-01

The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits.

Science.gov (United States)

Schiller, Alicia M; Pellegrino, Peter R; Zucker, Irving H

2016-01-15

Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits. Copyright © 2016 the American Physiological Society.

Early life stress sensitizes the renal and systemic sympathetic system in rats.

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Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Review of the State of Renal Nerve Ablation for Patients with Severe and Resistant Hypertension

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Gulati, Vinay; White, William B.

2013-01-01

Through modulation of renin secretion, glomerular filtration rate and renal absorption of sodium, the sympathetic innervation of the kidneys plays an important role in the pathogenesis of hypertension. Renal nerve ablation technology is being developed for treatment of drug-treatment resistant hypertension worldwide. Preliminary research with the use of radiofrequency based renal denervation systems have demonstrated encouraging results with significant reduction of blood pressure in patients inadequately controlled despite nearly maximal drug therapy regimens. From work done thus far, the renal denervation procedure has not been associated with serious adverse effects. Long term efficacy and safety still needs to be established for renal nerve ablation. This review focuses on the impact of the renal sympathetic system on blood pressure regulation, the clinical rationale for renal nerve ablation in severe and drug-treatment resistant hypertension and current evidence from the more advanced renal denervation devices. PMID:23953998

High specific radioactivity (1R,2S)-4-[18F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

International Nuclear Information System (INIS)

Langer, Oliver; Valette, Heric; Dolle, Frederic; Halldin, Christer; Loc'h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-01-01

The radiolabeled catecholamine analogue (1R,2S)-6-[ 18 F]fluorometaraminol (6-[ 18 F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[ 18 F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[ 18 F]fluorometaraminol (4-[ 18 F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/μmol). In the present study, we demonstrate in rats that 4-[ 18 F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[ 18 F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[ 18 F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[ 18 F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[ 18 F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[ 18 F]FMR is a promising alternative to 6-[ 18 F]FMR for myocardial neuronal mapping with PET in humans

[The influence of single moderate exercise on the sympathetic nervous system activity in patients with essential hypertension].

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Gajek, Jacek; Zyśko, Dorota

2002-12-01

Sympathetic nervous system may play an important role in development and maintenance of hypertension. Its activity can be assessed by plasma levels of catecholamines, neuropeptide Y (NPY) and adrenergic receptor density. Hypertensive subjects may be more prone to reveal overactivity of sympathetic nervous system, for instance as a result of physical stress. The aim of the study was to determine the activity of sympathetic nervous system in young patients with newly recognized, untreated mild hypertension. The study was carried out in 22 patients (age 38.5 +/- 10.3 years) and 20 normotensive volunteers (age 38.5 +/- 8.6 years) as a control group, matched for sex. Density of alpha 2- and beta-adrenergic receptors using 3H-yohimbine and 125I-cyanopindolol respectively, total catecholamines and plasma renin activity using radioenzymatic assay, neuropeptide Y and aldosterone using radioimmunoassay were assessed in the blood taken in the supine position and after moderate bicycle ergometer exercise. Plasma concentration of NPY at rest did not differ between the groups, but increased significantly after exercise and was greater in hypertensive patients (p < 0.05). The density of alpha 2- and beta-adrenergic receptors at rest and after exercise in hypertensive subjects was unchanged when comparing to healthy individuals. The plasma concentrations of endogenous catecholamines, plasma renin activity and aldosterone level increase during exercise in both studied groups (p < 0.05). Aldosterone level was higher in hypertensive patients at rest (p < 0.05). There was a negative correlation between baseline aldosterone and NPY levels in hypertensive patients (r = -0.44, p < 0.05). Moderate exercise in hypertensive subjects causes the hyperactivity of sympathetic nervous system expressed as increase of NPY plasma level.

Electrical modulation of the sympathetic nervous system in order to augment cerebral blood flow : a protocol for an experimental study

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Ter Laan, Mark; van Dijk, J. Marc C.; Staal, Michiel J.; Elting, Jan-Willem J.

2011-01-01

Introduction: Cerebral blood flow (CBF) is regulated by several mechanisms. Neurogenic control has been a matter of debate, even though several publications reported the effects of changes in sympathetic tone on CBF. Transcutaneous electrical nerve stimulation and spinal-cord stimulation have been

Alpha-Blocker Treatment Response in Men With Lower Urinary Tract Symptoms Based on Sympathetic Activity: Prospective, Multicenter, Open-Labeled, Observational Study

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Sung Gon Park

2015-06-01

Full Text Available Purpose: In this study, we compared the treatment outcomes for an α-blocker between 2 groups of men, one with high sympathetic activity (HSA and another with low sympathetic activity (LSA or normal sympathetic activity. Methods: A total of 159 men (≥50 years of age with lower urinary tract symptoms resulting from benign prostatic hyperplasia were analyzed. We assigned patients to groups according to their sympathetic activity, which was evaluated by heart ratevariability measurements. HSA was defined as a low frequency/high frequency ratio greater than 1.6. All patients received 10mg of alfuzosin once a day for 12 weeks. The primary end point was a change in the total International Prostate SymptomScore (IPSS at 12 weeks from baseline. Results: Sixty-seven men were assigned to the HSA group and 92 men were assigned to the LSA group. The baseline characteristics were not significantly different between the 2 groups, and the response to alfuzosin was good in both groups. Themean total IPSS change was not different between the groups. Both groups were not significantly different with respect to the changes in maximal flow rate, IPSS voiding or storage symptom subscores, quality of life, and rates of adverse drug events. TheHSA group showed a similar willingness to continue treatment compared to the LSA group, although their treatment satisfaction rating was lower. Conclusions: The therapeutic effects of alfuzosin did not differ in regards to the differences in sympathetic activity, but treatment satisfaction ratings were lower in the HSA group.

Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

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Suuronen Erik J

2011-08-01

Full Text Available Abstract Background Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. Methods Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED. Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET expression were evaluated as correlative measurements. Results The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. Conclusions Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system

Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

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J Preston Campbell

2012-07-01

Full Text Available Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

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Campbell, J Preston; Karolak, Matthew R; Ma, Yun; Perrien, Daniel S; Masood-Campbell, S Kathryn; Penner, Niki L; Munoz, Steve A; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A; Elefteriou, Florent

2012-07-01

Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

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Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

2015-01-01

Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

Sympathetic activity of S-(+-ketamine low doses in the epidural space

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Slobodan Mihaljevic

2014-07-01

Full Text Available BACKGROUND AND OBJECTIVES: S-(+-ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S-(+-ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S-(+-ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block. METHODS: The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine was given to one group (control group while local anaesthesia and S-(+-ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non-competitive enzyme immunochemistry method (Cat Combi ELISA was used to determine the concentrations of catecholamines (adrenaline and noradrenaline. Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann-Whitney U-test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects. RESULTS: 40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S-(+-ketamine. Value p < 0.05 has been taken as a limit of statistical significance. CONCLUSIONS: Low dose of S-(+-ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S-(+-ketamine administered epidurally did not deepen sympathetic block. Adding 25 mg of S-(+-ketamine to 0

Sympathetic stimulation alters left ventricular relaxation and chamber size.

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Burwash, I G; Morgan, D E; Koilpillai, C J; Blackmore, G L; Johnstone, D E; Armour, J A

1993-01-01

Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.

Perceptual consequences of disrupted auditory nerve activity.

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Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature

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Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D.; Keeble, Julie E.

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. PMID:26136480

Sympathetic vasoconstriction takes an unexpected pannexin detour

DEFF Research Database (Denmark)

Schak Nielsen, Morten

2015-01-01

Sympathetic vasoconstriction plays an important role in the control of blood pressure and the distribution of blood flow. In this issue of Science Signaling, Billaud et al. show that sympathetic vasoconstriction occurs through a complex scheme involving the activation of large-pore pannexin 1...... channels and the subsequent release of adenosine triphosphate that promotes contraction in an autocrine and paracrine manner. This elaborate mechanism may function as a point of intercept for other signaling pathways-for example, in relation to the phenomenon "functional sympatholysis," in which exercise...... abrogates sympathetic vasoconstriction in skeletal muscle. Because pannexin 1 channels are inhibited by nitric oxide, they may function as a switch to turn off adrenergic signaling in skeletal muscle during exercise....

Sympathetic arousal as a marker of chronicity in childhood stuttering.

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Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M

2018-01-01

This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.

High specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

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Langer, Oliver; Valette, Heric; Dolle, Frederic E-mail: dolle@dsvidf.cea.fr; Halldin, Christer; Loc' h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-04-01

The radiolabeled catecholamine analogue (1R,2S)-6-[{sup 18}F]fluorometaraminol (6-[{sup 18}F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[{sup 18}F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/{mu}mol). In the present study, we demonstrate in rats that 4-[{sup 18}F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[{sup 18}F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[{sup 18}F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[{sup 18}F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[{sup 18}F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[{sup 18}F]FMR is a promising alternative to 6-[{sup 18}F]FMR for myocardial neuronal mapping with PET in humans.

Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

NARCIS (Netherlands)

Kienbaum, P.; Heuter, T.; Michel, M. C.; Peters, J.

2000-01-01

BACKGROUND: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent

Sympathetic Nerves in Breast Cancer: Angiogenesis and Antiangiogenic Therapy

Science.gov (United States)

2013-02-01

an enzyme found only outside nerve terminals (6). We showed that splenic NE and NMN were markedly elevated 3 days after DMI implantation relative to...daily ISO treatment (Figs. 3A; attached manuscript day x treatment interaction, p = 0.14). To further investigate potential ß-AR-induced effects on...It has high affinity for ß2-AR, but is unable to desensitize ß-AR, resulting in a long-term effectiveness that cannot be achieved with most ß-agonists

Sympathetic neural modulation of the immune system

International Nuclear Information System (INIS)

Madden, K.S.

1989-01-01

One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

Role of sympathetic nervous system and neuropeptides in obesity hypertension

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J.E. Hall

2000-06-01

Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

Science.gov (United States)

Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Sympathetic and parasympathetic regulation of rectal motility in rats.

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Ridolfi, Timothy J; Tong, Wei-Dong; Takahashi, Toku; Kosinski, Lauren; Ludwig, Kirk A

2009-11-01

The colon and rectum are regulated by the autonomic nervous system (ANS). Abnormalities of the ANS are associated with diseases of the colon and rectum while its modulation is a putative mechanism for sacral nerve stimulation. The purpose of this study is to establish a rat model elucidating the role of the efferent ANS on rectal motility. Rectal motility following transection or stimulation of parasympathetic pelvic nerves (PN) or sympathetic hypogastric nerves (HGN) was measured with rectal strain gauge transducers and quantified as a motility index (MI). Colonic transit was measured 24 hours after transection by calculating the geometric center (GC) of distribution of (51)Cr Transection of PN and HGN decreased MI to 518 +/- 185 g*s (p < 0.05) and increased MI to 5,029 +/- 1,954 g*s (p < 0.05), respectively, compared to sham (975 +/- 243 g*s). Sectioning of PN and HGN decreased transit with GC = 4.9 +/- 0.2 (p < 0.05) and increased transit with GC = 8.1 +/- 0.7 (p < 0.02), respectively, compared to sham (GC = 5.8 +/- 0.3). Stimulation of PN and HGN increased MI to 831 +/- 157% (p < 0.01) and decreased MI to 251 +/- 24% (p < 0.05), respectively. Rectal motility is significantly altered by sectioning or stimulating either HGN or PN. This model may be useful in studying how sacral nerve stimulation exerts its effects and provide insight into the maladies of colonic motility.

Bioelectronic block of paravertebral sympathetic nerves mitigates post-myocardial infarction ventricular arrhythmias.

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Chui, Ray W; Buckley, Una; Rajendran, Pradeep S; Vrabec, Tina; Shivkumar, Kalyanam; Ardell, Jeffrey L

2017-11-01

Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT). To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI). In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation. CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Catheter based radiofrequency ablation of renal nerves for the treatment of resistant hypertension

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Markus P. Schlaich

2013-03-01

Full Text Available Introduction Resistant hypertension is a common and growing clinical problem characterized by the failure to attain target blood pressure levels despite adequate use of at least three antihypertensive agents. Objectives The aim of this article is to emphasize the role of novel approaches to treat resistant hypertension. Materials and methods After an excursus on the physiological role of renal nerves on kidney function, volume homeostasis and blood pressure control, this article describes the radiofrequency ablation technology to obtain kidneys denervation. Results Activation of the sympathetic nervous system plays a prominent role as a major regulator of circulatory and metabolic control. The kidneys have a particularly dense afferent sensory and efferent sympathetic innervation and are thereby strategically positioned to be origin as well as target of sympathetic activation. In this context, recent evidence suggests that a novel catheter-based approach to functionally denervate the human kidneys using radiofrequency ablation technology may provide a safe and effective treatment alternative for resistant hypertension and its adverse consequences. Conclusions Despite the availability of numerous safe and effective pharmacological therapies to treat elevated blood pressure, novel therapeutic approaches are warranted to improve the management and prognosis of patients with refractory hypertension. Several clinical trials are currently conducted and planned to further substantiate the blood pressure lowering efficacy of this novel renal denervation procedure.

[Improvement of approach to performance of lumbar sympathetic blockade in patients with tissue ischemia of the lower extremities].

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Panov, V M; Fesenko, U A; Kutsyn, V M

2014-06-01

New access for performance of sympathic blockade in region of aortal bifurcation, was elaborated, basing on calculations, conducted on 30 spiral computeric tomograms of lumbar and sacral parts of vertebral column. Application of the method permits to escape such complications, as a renal and the main vessels damage, the sympathetic nerves blockade, do not demand roentgenological control.

Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

NARCIS (Netherlands)

Kox, M.; Eijk, L.T.G.J. van; Zwaag, J.; Wildenberg, J. van den; Sweep, F.C.; Hoeven, J.G. van der; Pickkers, P.

2014-01-01

Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot

Expression of adenosine triphosphate-sensitive potassium channels in rats with cirrhosis: correlationship with sympathetic activity and renal function

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Julio Cesar Martins Monte

2006-12-01

Full Text Available Objective: The aim of this study was to perform a direct analysis ofKATP mRNA expression by RT-PCR in kidney and isolated aorta fromrats with cirrhosis (induced by carbon tetrachloride and controls.The present study also analyses the relation between induced cirrhosisand urinary excretion of sodium and sympathetic activity in cirrhoticrats. Methods: Rats were placed in metabolic cages and allowedfree access to food and water. Cirrhosis was induced by repeateddoses of carbon tetrachloride by gastric gavage. After some weeks,the kidney and aorta were dissected and utilized for RNA extraction.Blood and urine were analyzed for electrolytes. Renal function wasestimated by creatinine clearance and sodium urinary excretion.Serum catecholamines were measured by HPLC analysis. Results:First, RT-PCR analysis showed that KATP mRNA is expressed in liverwith cirrhosis and intense fibrosis, but not with moderate fibrosis.Second, RT-PCR analysis revealed that KATP mRNA was detectedonly in aorta dissected from rats with cirrhosis. Finally, an enhancedreabsorption of sodium without renal failure suggests a potentialmediator would increase the activity of the sympathetic system.Conclusion: These results suggest that KATP mRNA is expressed incirrhotic rats with sympathetic activation and renal dysfunction. Thischannel might be involved in another route where the vascular tonecan be modulated in cirrhosis.

Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

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Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

2015-03-01

An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

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Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

2003-05-01

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

NARCIS (Netherlands)

Benthem, L; Keizer, Klaas-Jan; Wiegman, CH; De Boer, SF; Strubbe, JH; Steffens, AB; Kuipers, F; Scheurink, AJW

2000-01-01

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the

Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control : A Longitudinal Study

NARCIS (Netherlands)

Licht, Carmilla M. M.; Penninx, Brenda W. J. H.; de Geus, Eco J. C.

2012-01-01

Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of

Pituitary adenylate cyclase-activating polypeptide stimulates glucose production via the hepatic sympathetic innervation in rats.

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Yi, Chun-Xia; Sun, Ning; Ackermans, Mariette T; Alkemade, Anneke; Foppen, Ewout; Shi, Jing; Serlie, Mireille J; Buijs, Ruud M; Fliers, Eric; Kalsbeek, Andries

2010-07-01

The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. Intracerebroventricular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production.

Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

DEFF Research Database (Denmark)

Eldrup, E; Christensen, N J; Andreasen, J

1989-01-01

in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...... in diabetics without neuropathy, and 6.85 (5.58-7.36, n = 8) nmol l-1 in controls. No relationship was obtained between baseline values of plasma NE and plasma DOPA. Plasma DOPA did not change in the upright position, whereas plasma NE increased significantly. Our results indicate that plasma DOPA...... is not related to sympathetic activity and may be of non-neuronal origin....

Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

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Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

2008-01-01

The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

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Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

Contribution of α-adrenoceptors to depolarization and contraction evoked by continuous asynchronous sympathetic nerve activity in rat tail artery

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Brock, J A; McLachlan, E M; Rayner, S E

1997-01-01

The effects of continuous but asynchronous nerve activity induced by ciguatoxin (CTX-1) on the membrane potential and contraction of smooth muscle cells have been investigated in rat proximal tail arteries isolated in vitro. These effects have been compared with those produced by the continuous application of phenylephrine (PE).CTX-1 (0.4 nM) and PE (10 μM) produced a maintained depolarization of the arterial smooth muscle that was almost completely blocked by α-adrenoceptor blockade. In both cases, the depolarization was more sensitive to the selective α2-adrenoceptor antagonist, idazoxan (0.1 μM), than to the selective α1-adrenoceptor antagonist, prazosin (0.01 μM).In contrast, the maintained contraction of the tail artery induced by CTX-1 (0.2 nM) and PE (2 and 10 μM) was more sensitive to prazosin (0.01) μM, than to idazoxan (0.01 μM). In combination, these antagonists almost completely inhibited contraction to both agents.Application of the calcium channel antagonist, nifedipine (1 μM), had no effect on the depolarization induced by either CTX-1 or PE but maximally reduced the force of the maintained contraction to both agents by about 50%.We conclude that the constriction of the tail artery induced by CTX-1, which mimics the natural discharge of postganglionic perivascular axons, is due almost entirely to α-adrenoceptor activation. The results indicate that neuronally released noradrenaline activates more than one α-adrenoceptor subtype. The depolarization is dependent primarily on α2-adrenoceptor activation whereas the contraction is dependent primarily on α1-adrenoceptor activation. The links between α-adrenoceptor activation and the voltage-dependent and voltage-independent mechanisms that deliver Ca2+ to the contractile apparatus appear to be complex. PMID:9113373

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

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Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-03-19

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

RESTING SYMPATHETIC BAROREFLEX SENSITIVITY IN SUBJECTS WITH LOW AND HIGH TOLERANCE TO CENTRAL HYPOVOLEMIA INDUCED BY LOWER BODY NEGATIVE PRESSURE

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Carmen eHinojosa-Laborde

2014-06-01

Full Text Available Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock. The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA and sympathetic baroreflex sensitivity (BRS are attenuated in male and female subjects who have low tolerance (LT to central hypovolemia induced by lower body negative pressure (LBNP. MSNA and diastolic arterial pressure (DAP were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms. LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28, and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats-1•mmHg-1, p=0.29. We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS.

Electroejaculation functions primarily by direct activation of pelvic musculature: Perspectives from a porcine model

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Adam M.R. Groh

2018-03-01

Full Text Available Ejaculatory dysfunction is a significant cause of infertility in men that have incurred spinal cord injury or iatrogenic lesions to the sympathetic nerves in the retroperitoneum. For such patients, electroejaculation – whereby a voltage is applied transrectally under general anesthesia – is a highly-effective procedure to obtain ejaculate. At present, however, there remains uncertainty as to the physiological mechanism by which electroejaculation prompts seminal emission in males with neurogenic anejaculation. Thus, in the present study, we aimed to determine, for the first time, whether electroejaculation functions by mimicking a neurophysiological response, or by directly activating local pelvic musculature. Using electroejaculation in a novel porcine model, we monitored the strength of contraction of the internal urethral sphincter (a smooth muscle involved in ejaculation before and after lesioning its sympathetic innervation with a combination of progressively-worsening surgical and pharmacological insults in three anesthetized boars (46.1 ± 7.4 kg. Importantly, prior to this investigation, we confirmed the comparative structural anatomy of the porcine model to humans through gross dissection and histological analysis of the infrarenal retroperitoneal sympathetic nerves and ganglia in 18 unembalmed boars. Prior to sacrifice, three of these boars underwent functional testing to confirm control of the internal urethral sphincter by the hypogastric nerves. Our results demonstrate that electroejaculation-induced contraction of the internal urethral sphincter was preserved following each progressive neural insult compared to the control state (p > 0.05. In contrast, these same insults resulted in paralysis/paresis of the internal urethral sphincter when its sympathetic innervation was directly stimulated with bipolar electrodes (p < 0.05. Taken together, our results provide the first empirical evidence to suggest that

The modulation of visceral functions by somatic afferent activity.

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Sato, A; Schmidt, R F

1987-01-01

We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

A model-based approach for the evaluation of vagal and sympathetic activities in a newborn lamb.

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Le Rolle, Virginie; Ojeda, David; Beuchée, Alain; Praud, Jean-Paul; Pladys, Patrick; Hernández, Alfredo I

2013-01-01

This paper proposes a baroreflex model and a recursive identification method to estimate the time-varying vagal and sympathetic contributions to heart rate variability during autonomic maneuvers. The baroreflex model includes baroreceptors, cardiovascular control center, parasympathetic and sympathetic pathways. The gains of the global afferent sympathetic and vagal pathways are identified recursively. The method has been validated on data from newborn lambs, which have been acquired during the application of an autonomic maneuver, without medication and under beta-blockers. Results show a close match between experimental and simulated signals under both conditions. The vagal and sympathetic contributions have been simulated and, as expected, it is possible to observe different baroreflex responses under beta-blockers compared to baseline conditions.

Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome

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Elisabeth eLambert

2014-07-01

Full Text Available Orthostatic intolerance is the inability to tolerate the upright posture and is relieved by recumbence. It most commonly affects young women and has a major impact on quality of life and psychosocial well being. Several forms of orthostatic intolerance have been described. The most common one is the recurrent vasovagal syncope (VVS phenotype which presents as a transient and abrupt loss of consciousness and postural tone that is followed by rapid recovery. Another common type of orthostatic intolerance is the postural orthostatic tachycardia syndrome (POTS which is characterized by an excessive rise in heart rate upon standing and is associated with symptoms of presyncope such as light-headedness, fatigue, palpitations and nausea. Maintenance of arterial pressure under condition of reduced central blood volume during the orthostasis is accomplished in large part through sympathetic efferent nerve traffic to the peripheral vasculature. Therefore sympathetic nervous system (SNS dysfunction is high on the list of possible contributors to the pathophysiology of orthostatic intolerance. Investigations into the role of the SNS in orthostatic intolerance have yielded mixed results. This review outlines the current knowledge of the function of the SNS in both VVS and POTS.

1.5 T augmented reality navigated interventional MRI: paravertebral sympathetic plexus injections.

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Marker, David R; U Thainual, Paweena; Ungi, Tamas; Flammang, Aaron J; Fichtinger, Gabor; Iordachita, Iulian I; Carrino, John A; Fritz, Jan

2017-01-01

The high contrast resolution and absent ionizing radiation of interventional magnetic resonance imaging (MRI) can be advantageous for paravertebral sympathetic nerve plexus injections. We assessed the feasibility and technical performance of MRI-guided paravertebral sympathetic injections utilizing augmented reality navigation and 1.5 T MRI scanner. A total of 23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%), and hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA-enhanced saline was injected. Outcome variables included the number of control magnetic resonance images, target error of the needle tip, punctures of critical nontarget structures, distribution of the injected fluid, and procedure length. Augmented-reality navigated MRI guidance at 1.5 T provided detailed anatomical visualization for successful targeting of the paravertebral space, needle placement, and perineural paravertebral injections in 46 of 46 targets (100%). A mean of 2 images (range, 1-5 images) were required to control needle placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and changes of needle advancement occurred in 6 of 46 targets (13%), which were statistically not related to spinal regions (P = 0.728 and P = 0.86, respectively) and cadaver sizes (P = 0.893 and P = 0.859, respectively). The mean error of the needle tip was 3.9±1.7 mm. There were no punctures of critical nontarget structures. The mean procedure length was 33±12 min. 1.5 T augmented reality-navigated interventional MRI can provide accurate imaging guidance for perineural injections of the thoracic, lumbar, and hypogastric sympathetic plexus.

Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge

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Porta, Alberto; Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias

2017-05-01

The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Theobromine inhibits sensory nerve activation and cough.

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Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J

2005-02-01

Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors

DEFF Research Database (Denmark)

Gnad, Thorsten; Scheibler, Saskia; von Kügelgen, Ivar

2014-01-01

hamster or rat. However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A2A...

Reduction of Blood Pressure Following After Renal Artery Adventitia Stripping During Total Nephroureterectomy: Potential Effect of Renal Sympathetic Denervation.

Science.gov (United States)

Okamura, Keisuke; Satou, Shunsuke; Setojima, Keita; Shono, Shinjiro; Miyajima, Shigero; Ishii, Tatsu; Shirai, Kazuyuki; Urata, Hidenori

2018-05-16

BACKGROUND Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. CASE REPORT Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. CONCLUSIONS A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

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Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

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Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

2015-12-01

Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

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Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

2018-01-01

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Peripheral nerve injury induces glial activation in primary motor cortex

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Julieta Troncoso

2015-02-01

Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

alfa-Amylase as a reliable and convenient measure of sympathetic activity: don’t start salivating just yet!

NARCIS (Netherlands)

Bosch, JA; Veerman, J.W.; de Geus, E.J.C.; Proctor, J.

2011-01-01

Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which

α-Amylase as a reliable and convenient measure of sympathetic activity: don't start salivating just yet!

NARCIS (Netherlands)

Bosch, J.A.; Veerman, E.C.I.; de Geus, E.J.; Proctor, G.B.

2011-01-01

Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which

Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity.

Science.gov (United States)

Nogueiras, Ruben; Pérez-Tilve, Diego; Veyrat-Durebex, Christelle; Morgan, Donald A; Varela, Luis; Haynes, William G; Patterson, James T; Disse, Emmanuel; Pfluger, Paul T; López, Miguel; Woods, Stephen C; DiMarchi, Richard; Diéguez, Carlos; Rahmouni, Kamal; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H

2009-05-06

We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.

Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

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Lauto, A; Trickett, R; Malik, R; Dawes, J M; Owen, E R

1997-01-01

Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

Carotid body (Thermoreceptors, sympathetic neural activation, and cardiometabolic disease

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Rodrigo Iturriaga

Full Text Available The carotid body (CB is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.

Neural correlates of fear-induced sympathetic response associated with the peripheral temperature change rate.

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Yoshihara, Kazufumi; Tanabe, Hiroki C; Kawamichi, Hiroaki; Koike, Takahiko; Yamazaki, Mika; Sudo, Nobuyuki; Sadato, Norihiro

2016-07-01

Activation of the sympathetic nervous system is essential for coping with environmental stressors such as fearful stimuli. Recent human imaging studies demonstrated that activity in some cortical regions, such as the anterior cingulate cortex (ACC) and anterior insula cortex (aIC), is related to sympathetic activity. However, little is known about the functional brain connectivity related to sympathetic response to fearful stimuli. The participants were 32 healthy, right-handed volunteers. Functional magnetic resonance imaging (fMRI) was used to examine brain activity when watching horror and control movies. Fingertip temperature was taken during the scanning as a measure of sympathetic response. The movies were watched a second time, and the degree of fear (9-point Likert-type scale) was evaluated every three seconds. The brain activity of the ACC, bilateral aIC, and bilateral anterior prefrontal cortex (aPFC) was correlated with the change rate of fingertip temperature, with or without fearful stimuli. Functional connectivity analysis revealed significantly greater positive functional connectivity between the amygdala and the ACC and between the amygdala and the aIC when watching the horror movie than when watching the control movie. Whole-brain psycho-physiological interaction (PPI) analysis revealed that the functional connectivity between the left amygdala and the ACC was modulated according to the fear rating. Our results indicate that the increased functional connectivity between the left amygdala and the ACC represents a sympathetic response to fearful stimuli. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Coordinated Respiratory Motor Activity in Nerves Innervating the Upper Airway Muscles in Rats.

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Satoshi Tachikawa

Full Text Available Maintaining the patency of the upper airway during breathing is of vital importance. The activity of various muscles is related to the patency of the upper airway. In the present study, we examined the respiratory motor activity in the efferent nerves innervating the upper airway muscles to determine the movements of the upper airway during respiration under normocapnic conditions (pH = 7.4 and in hypercapnic acidosis (pH = 7.2. Experiments were performed on arterially perfused decerebrate rats aged between postnatal days 21-35. We recorded the efferent nerve activity in a branch of the cervical spinal nerve innervating the infrahyoid muscles (CN, the hypoglossal nerve (HGN, the external branch of the superior laryngeal nerve (SLN, and the recurrent laryngeal nerve (RLN with the phrenic nerve (PN. Inspiratory nerve discharges were observed in all these nerves under normocapnic conditions. The onset of inspiratory discharges in the CN and HGN was slightly prior to those in the SLN and RLN. When the CO2 concentration in the perfusate was increased from 5% to 8% to prepare for hypercapnic acidosis, the peak amplitudes of the inspiratory discharges in all the recorded nerves were increased. Moreover, hypercapnic acidosis induced pre-inspiratory discharges in the CN, HGN, SLN, and RLN. The onset of pre-inspiratory discharges in the CN, HGN, and SLN was prior to that of discharges in the RLN. These results suggest that the securing of the airway that occurs a certain time before dilation of the glottis may facilitate ventilation and improve hypercapnic acidosis.

Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

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Hopper, Ingrid; Gronda, Edoardo; Hoppe, Uta C; Rundqvist, Bengt; Marwick, Thomas H; Shetty, Sharad; Hayward, Christopher; Lambert, Thomas; Hering, Dagmara; Esler, Murray; Schlaich, Markus; Walton, Antony; Airoldi, Flavio; Brandt, Mathias C; Cohen, Sidney A; Reiters, Pascalle; Krum, Henry

2017-09-01

Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min -1  • 1.73 m -2 ; P= .700). RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study. Copyright © 2017 Elsevier Inc. All rights reserved.

AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

NARCIS (Netherlands)

GEERTZEN, JHB; EISMA, WH

Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

Energy Technology Data Exchange (ETDEWEB)

AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman, Av. Roca 2200, PC 4000 (Argentina); Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina)

2007-11-15

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

International Nuclear Information System (INIS)

AlbarracIn, A L; Farfan, F D; Felice, C J

2007-01-01

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle

Sympathetic activity of S-(+-ketamine low doses in the epidural space

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Slobodan Mihaljevic

2014-07-01

ística. Conclusões: dose baixa de cetamina S-(+ administrada por via epidural não teve efeitos simpaticomiméticos; não alterou a pressão arterial, o pulso, os hormônios séricos ou o tempo de transição de pulso. Dose baixa de cetamina S-(+ administrada por via epidural não aprofundou o bloqueio simpático. A adição de 25 mg de cetamina S-(+ à bupivacaína a 0,5% não deprimiu o tônus simpático abaixo do nível do bloqueio peridural no momento máximo de bloqueio simpático e não tem efeito sobre o tônus simpático acima do nível do bloqueio. Keywords: S-(+-ketamine, Epidural space, Low doses, Sympathetic activity, Palavras-chave: Cetamina S-(+, Espaço epidural, Doses baixas, Atividade simpática

Stress and Female Reproductive System: Disruption of Corticotropin-Releasing Hormone/Opiate Balance by Sympathetic Nerve Traffic

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Farideh Zafari Zangeneh

2009-09-01

Full Text Available Nowadays stress is an integral part of everyday living and the physiological and behavioral consequences of exposure to stressful situations have been extensively studied for decades. The stress response is a necessary mechanism but disrupts homeostatic process and it is sub served by a complex system located in both the central nervous system (CNS and the periphery. Stressor-induced activation of the hypothalamus–pituitary–adrenal (HPA axis and the sympathetic nervous system (SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Normal activation of the HPA axis is essential for reproduction, growth, metabolic homeostasis, and responses to stress and they are critical for adapting to changes in the external environment. The regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classical feedback mechanisms in the hypothalamus and the pituitary. The present overview focuses on the neuroendocrine infrastructure of the adaptive response to stress and its effects on the female reproductive system. 

Patterns of motor activity in the isolated nerve cord of the octopus arm.

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Gutfreund, Yoram; Matzner, Henry; Flash, Tamar; Hochner, Binyamin

2006-12-01

The extremely flexible octopus arm provides a unique opportunity for studying movement control in a highly redundant motor system. We describe a novel preparation that allows analysis of the peripheral nervous system of the octopus arm and its interaction with the muscular and mechanosensory elements of the arm's intrinsic muscular system. First we examined the synaptic responses in muscle fibers to identify the motor pathways from the axial nerve cord of the arm to the surrounding musculature. We show that the motor axons project to the muscles via nerve roots originating laterally from the arm nerve cord. The motor field of each nerve is limited to the region where the nerve enters the arm musculature. The same roots also carry afferent mechanosensory information from the intrinsic muscle to the axial nerve cord. Next, we characterized the pattern of activity generated in the dorsal roots by electrically stimulating the axial nerve cord. The evoked activity, although far reaching and long lasting, cannot alone account for the arm extension movements generated by similar electrical stimulation. The mismatch between patterns of activity in the isolated cord and in an intact arm may stem from the involvement of mechanosensory feedback in natural arm extension.

Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo

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Daisuke Kajimura

2014-10-01

Full Text Available The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1Dbh−/− display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1Dbh−/− mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

Somatosympathetic vasoconstrictor reflexes in human spinal cord injury: responses to innocuous and noxious sensory stimulation below lesion

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Vaughan G Macefield

2012-06-01

Full Text Available It is known that the sudden increases in blood pressure associated with autonomic dysreflexia in people with spinal cord injury (SCI is due to a spinally-mediated reflex activation of sympathetic vasoconstrictor neurones supplying skeletal muscle and the gut. Apart from visceral inputs, such as those originating from a distended bladder, there is a prevailing opinion that autonomic dysreflexia can be triggered by noxious stimulation below the lesion. However, do noxious inputs really cause an increase in blood pressure in SCI? Using microelectrodes inserted into a peripheral nerve to record sympathetic nerve activity we had previously shown that selective stimulation of small-diameter afferents in muscle or skin, induced by bolus injection of hypertonic saline into the tibialis anterior muscle or the overlying skin, evokes a sustained increase in muscle sympathetic nerve activity and blood pressure and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow. We postulated that these sympathetic responses would be exaggerated in SCI, with a purely noxious stimulus causing long-lasting increases in blood pressure and long-lasting decreases in skin blood flow. Surprisingly, though, we found that intramuscular or subcutaneous injection of hypertonic saline into the leg caused negligible changes in these parameters. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, caused a marked increase in blood pressure in SCI but not in able-bodied subjects. This suggests that it is activation of large-diameter somatic afferents, not small-diameter afferents, that triggers increases in sympathetic outflow in SCI. Whether the responses to activation of large-diameter afferents reflect plastic changes in the spinal cord in SCI is unknown.

Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

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Kadow, Brian T; Lyon, Timothy D; Zhang, Zhaocun; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

2016-07-01

This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition. Copyright © 2016 the American Physiological Society.

Evidence that central dopamine receptors modulate sympathetic neuronal activity to the adrenal medulla to alter glucoregulatory mechanisms.

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Arnerić, S P; Chow, S A; Bhatnagar, R K; Webb, R L; Fischer, L J; Long, J P

1984-02-01

Previous reports suggest that analogs of dopamine (DA) can produce hyperglycemia in rats by interacting with DA receptors. Experiments reported here indicate the site of action and describe the metabolic sequalae associated with the hyperglycemic effect of apomorphine (APO), produced in conscious unrestrained rats. Apomorphine was more potent when administered by intracerebroventricular (i.c.v.) injection than when given subcutaneously (s.c.). Very small doses of the DA receptor antagonist pimozide, given intraventricularly, blocked the hyperglycemic effect of apomorphine administered subcutaneously. Sectioning of the spinal cord at thoracic vertebra T1-2 or sectioning the greater splanchnic nerve blocked apomorphine-induced hyperglycemia; whereas section of the superior colliculus or section at T5-6 had no effect. A dose of apomorphine or epinephrine (EPI) producing a similar degree of hyperglycemia elevated the concentration of EPI in serum to a similar degree, and the increase in EPI in serum preceded the increase in glucose in serum. Fasting animals for 2 or 18 hr had no significant effect on EPI- or apomorphine-induced hyperglycemia despite a reduction (91-93%) of the glycogen content of liver and skeletal muscle during the 18 hr fast. 5-Methoxyindole-2-carboxylic acid (MICA), an inhibitor of gluconeogenesis, blocked EPI- and apomorphine-induced hyperglycemia in rats fasted for 18 hr. However, 5-methoxyindole-2-carboxylic acid was ineffective in blocking hyperglycemia in animals fasted for 2 hr. Changes in insulin or glucagon in serum alone cannot account for the hyperglycemic action of apomorphine. These data demonstrate that apomorphine interacts with central DA receptors located in the hindbrain to activate sympathetic neuronal activity to the adrenal gland which subsequently releases epinephrine to alter homeostasis of glucose. Epinephrine may then, depending on the nutritional status, facilitate glycogenolytic or gluconeogenic processes to produce

Renal sympathetic denervation in the treatment of resistant hypertension.

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Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

2014-12-01

Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17 mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.

Nerve transection repair using laser-activated chitosan in a rat model.

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Bhatt, Neel K; Khan, Taleef R; Mejias, Christopher; Paniello, Randal C

2017-08-01

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Activity-dependent intracellular Ca2+ transients in unmyelinated nerve fibres of the isolated adult rat vagus nerve.

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Wächtler, J; Mayer, C; Grafe, P

1998-04-01

Confocal laser scanning microscopy was used to follow changes in the free intracellular calcium concentration ([Ca2+]i) in nerve fibres and adjacent Schwann cells in isolated rat vagus nerves. [Ca2+]i was monitored by the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during repetitive (1-50 Hz) supramaximal electrical stimulation or by bath application of ATP. Trains of action potentials were more effective at elongated, fibre-like structures of the vagus nerves, whereas ATP-induced Ca2+ transients were found predominantly in regions of Schwann cell bodies. Activity-induced Ca2+ signals were unaffected by pharmacological manipulation of intracellular Ca2+ stores, during long-lasting application of purinergic receptor agonists, or by substitution of extracellular Na+ with Li+. However, they were abolished in the presence of Ca2+-free bathing solution or after the blocking of Ca2+ channels with Cd2+. Ca2+ transients were also observed during Ca2+ action potentials. Such "Ca2+ spikes" were elicited by electrical stimulation in the presence of a combination of tetrodotoxin and K+ channel blockers. These data suggest that voltage-dependent Ca2+ channels, activated during short trains of Na+ action potentials, produce an increase in intra-axonal [Ca2+] of rat vagus nerves. We did not find evidence for activity-dependent Ca2+ transients in the Schwann cells surrounding the unmyelinated axons.

MR-guided Periarterial Ethanol Injection for Renal Sympathetic Denervation: A Feasibility Study in Pigs

International Nuclear Information System (INIS)

Streitparth, F.; Walter, A.; Stolzenburg, N.; Heckmann, L.; Breinl, J.; Rinnenthal, J. L.; Beck, A.; De Bucourt, M.; Schnorr, J.; Bernhardt, U.; Gebauer, B.; Hamm, B.; Günther, R. W.

2013-01-01

Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

MR-guided Periarterial Ethanol Injection for Renal Sympathetic Denervation: A Feasibility Study in Pigs

Energy Technology Data Exchange (ETDEWEB)

Streitparth, F., E-mail: florian.streitparth@charite.de; Walter, A.; Stolzenburg, N.; Heckmann, L.; Breinl, J. [Charite, Humboldt University, Department of Radiology (Germany); Rinnenthal, J. L. [Charite, Humboldt University, Department of Neuropathology (Germany); Beck, A.; De Bucourt, M.; Schnorr, J. [Charite, Humboldt University, Department of Radiology (Germany); Bernhardt, U. [InnoRa GmbH (Germany); Gebauer, B.; Hamm, B.; Guenther, R. W. [Charite, Humboldt University, Department of Radiology (Germany)

2013-06-15

Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

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Ploj Karolina

2005-09-01

Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. Methods Our objectives in this study were (1 to estimate sympathetic-adrenal medullary (SAM activity by measuring mean systolic blood pressure (MSAP in rats with estradiol valerate (EV-induced PCO; (2 to estimate alpha1a and alpha2a adrenoceptor expression in a brain area thought to mediate central effects on MSAP regulation and in the adrenal medulla; (3 to assess hypothalamic-pituitary-adrenal (HPA axis regulation by measuring adrenocorticotropic hormone (ACTH and corticosterone (CORT levels in response to novel-environment stress; and (4 to measure abdominal obesity, sex steroids, and insulin sensitivity. Results The PCO rats had significantly higher MSAP than controls, higher levels of alpha1a adrenoceptor mRNA in the hypothalamic paraventricular nucleus (PVN, and lower levels of alpha2a adrenoceptor mRNA in the PVN and adrenal medulla. After exposure to stress, PCO rats had higher ACTH and CORT levels. Plasma testosterone concentrations were lower in PCO rats, and no differences in insulin sensitivity or in the weight of intraabdominal fat depots were found. Conclusion Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism. These findings may have implications for mechanisms underlying hypertension in PCOS.

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

Science.gov (United States)

Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease.

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Eckelman, William C; Dilsizian, Vasken

2015-06-01

Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Vagal and sympathetic activity in burnouts during a mentally demanding workday

NARCIS (Netherlands)

Zanstra, Ydwine J.; Schellekens, Jan M. H.; Schaap, Cas; Kooistra, Libbe

2006-01-01

Objective: We study differences in task performance and related sympathetic-vagal reaction patterns between burnouts and controls during a mentally demanding workday. Method: Thirty-nine adults with burnout and 40 healthy controls performed mental tasks during a simulated workday. At pretest, just

Reinnervation following catheter-based radio-frequency renal denervation.

Science.gov (United States)

Booth, Lindsea C; Nishi, Erika E; Yao, Song T; Ramchandra, Rohit; Lambert, Gavin W; Schlaich, Markus P; May, Clive N

2015-04-20

What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation

Sensorimotor peripheral nerve function and physical activity in older men

DEFF Research Database (Denmark)

Lange-Maia, B. S.; Cauley, J A; Newman, Anne B

2016-01-01

We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n = 328, age 78.8 ± 4.7 years) conducted PN testing, including: peroneal motor and sural sensory nerve conduction...... (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monoflament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly [PASE] and SenseWear Armband). After...

Learned helplessness and responses to nerve blocks in chronic low back pain patients.

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Chapman, S L; Brena, S F

1982-01-01

In a double-blind study, 67 chronic low back pain patients received 4 lumbar sympathetic nerve blocks, two given with bupivacaine and two given with saline. It was hypothesized that patients showing evidence of 'learned helplessness,' as measured by dependence on habit-forming medications for the pain, low activity levels, and elevated MMPI scores on Hypochondriasis, Depression and Hysteria would show the least reduction in subjective pain intensity following injections with both bupivacaine and saline. It also was hypothesized that placebo responses would be greatest in patients who had a high educational level, were divorced, and had no pending disability claims. Responses 30 min following nerve blocks failed to correlate with these variables. However, decreases in subjective pain intensity 24 h following both types of nerve blocks were greater in patients who showed low levels of pain behavior, who were divorced, and who had no pending disability claims. Decreased pain 24 h following saline injections was significantly related to low scores on the Lie, Defensiveness, Hypochondriasis, and Hysteria scales of the MMPI and to reduced subjective pain intensity following a 6 week comprehensive outpatient pain rehabilitation program. It was concluded that chronic pain patients who are fixed in their focus on pain, high in pain-related behaviors, and low in responsibilities are less likely to respond favorably to nerve blocks and that medical treatment for them needs to be paired with therapies designed to reduce their helplessness.

Development of Kinematic Graphs of Median Nerve during Active Finger Motion: Implications of Smartphone Use.

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Hoi-Chi Woo

Full Text Available Certain hand activities cause deformation and displacement of the median nerve at the carpal tunnel due to the gliding motion of tendons surrounding it. As smartphone usage escalates, this raises the public's concern whether hand activities while using smartphones can lead to median nerve problems.The aims of this study were to 1 develop kinematic graphs and 2 investigate the associated deformation and rotational information of median nerve in the carpal tunnel during hand activities.Dominant wrists of 30 young adults were examined with ultrasonography by placing a transducer transversely on their wrist crease. Ultrasound video clips were recorded when the subject performing 1 thumb opposition with the wrist in neutral position, 2 thumb opposition with the wrist in ulnar deviation and 3 pinch grip with the wrist in neutral position. Six still images that were separated by 0.2-second intervals were then captured from the ultrasound video for the determination of 1 cross-sectional area (CSA, 2 flattening ratio (FR, 3 rotational displacement (RD and 4 translational displacement (TD of median nerve in the carpal tunnel, and these collected information of deformation, rotational and displacement of median nerve were compared between 1 two successive time points during a single hand activity and 2 different hand motions at the same time point. Finally, kinematic graphs were constructed to demonstrate the mobility of median nerve during different hand activities.Performing different hand activities during this study led to a gradual reduction in CSA of the median nerve, with thumb opposition together with the wrist in ulnar deviation causing the greatest extent of deformation of the median nerve. Thumb opposition with the wrist in ulnar deviation also led to the largest extent of TD when compared to the other two hand activities of this study. Kinematic graphs showed that the motion pathways of median nerve during different hand activities were complex

Skin conductance at baseline and postheel lance reflects sympathetic activation in neonatal opiate withdrawal.

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Oji-Mmuo, Christiana N; Michael, Eric J; McLatchy, Jacqueline; Lewis, Mary M; Becker, Julie E; Doheny, Kim Kopenhaver

2016-03-01

Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). Fourteen term (mean, SE: 38.8 ± 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/seconds and mean of peaks) was measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). Nonparametric tests were used to determine group differences, phase differences from baseline to HLS and HLS to recovery, and associations between MFNSS and SC measures. Neonates that would later require morphine treatment for NAS (n = 6) had higher baseline SC mean of peaks than those that did not require treatment (n = 8) (p < 0.05). Moreover, there were unique phase differences between groups and SC positively correlated with MFNSS (p < 0.05). SC provides early identification of NAS severity. However, a larger sample is needed to determine sensitivity and specificity of SC for early identification of NAS and treatment effectiveness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

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Kreipke, R E; Birren, S J

2015-12-01

Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

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Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

NARCIS (Netherlands)

Ballé, C.; Beuers, U.; ENGELHARDT, R.; JUNGERMANN, K.

1987-01-01

In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were

Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report

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Nwaejike Nnamdi

2008-06-01

Full Text Available Abstract Introduction Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. Case presentation We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Conclusion Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

Fibromyalgia: When Distress Becomes (Un)sympathetic Pain

OpenAIRE

Martinez-Lavin, Manuel

2012-01-01

Fibromyalgia is a painful stress-related disorder. A key issue in fibromyalgia research is to investigate how distress could be converted into pain. The sympathetic nervous system is the main element of the stress response system. In animal models, physical trauma, infection, or distressing noise can induce abnormal connections between the sympathetic nervous system and the nociceptive system. Dorsal root ganglia sodium channels facilitate this type of sympathetic pain. Similar mechanisms may...

Burst Activity and Heart Rhythm Modulation in the Sympathetic Outflow to the Heart

National Research Council Canada - National Science Library

Baselli, G

2001-01-01

In 13 decerebrate, artificially ventilated cats preganglionic sympathetic outflow to the heart was recorded with ECG and ventilation signal, A novel algorithm was implemented that extracts weighted...

Comparable attenuation of sympathetic nervous system activity in obese subjects with normal glucose tolerance, impaired glucose tolerance and treatment naïve type 2 diabetes following equivalent weight loss

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Nora E. Straznicky

2016-11-01

Full Text Available Background and Purpose: Elevated sympathetic nervous system (SNS activity is a characteristic of obesity and type 2 diabetes (T2D that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n=15, impaired glucose tolerant (IGT, n=24 and newly-diagnosed T2D (n=15 consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate for 4-months. The three groups were matched for baseline age (56 + 1 years, body mass index (BMI, 32.9 + 0.7 kg/m2 and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography, spontaneous cardiac baroreflex sensitivity (BRS and oral glucose tolerance test. Results: Weight loss averaged -7.5 + 0.8, -8.1 + 0.5 and -8.0 + 0.9 % of body weight in NGT, IGT and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120 compared to NGT and IGT (group effect, P<0.001. Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group x time, P=0.04. The magnitude of reduction in MSNA (-7 + 3, -8 + 4, -15 + 4 burst/100hb, respectively and whole-body norepinephrine spillover rate (-28 + 8, -18 + 6 and -25 + 7 %, respectively, time effect both P<0.001, did not differ between groups. After adjustment for age and change in body weight, ∆ insulin AUC0-120 was independently associated with reduction in arterial norepinephrine concentration, whilst ∆ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance

Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

Science.gov (United States)

Raffel, D M; Corbett, J R; del Rosario, R B; Gildersleeve, D L; Chiao, P C; Schwaiger, M; Wieland, D M

1996-12-01

The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

SYMPATHETIC FILAMENT ERUPTIONS FROM A BIPOLAR HELMET STREAMER IN THE SUN

International Nuclear Information System (INIS)

Yang Jiayan; Jiang Yunchun; Zheng Ruisheng; Bi Yi; Hong Junchao; Yang Bo

2012-01-01

On 2005 August 5, two solar filaments erupted successively from different confined arcades underlying a common overarching multiple-arcade bipolar helmet streamer. We present detailed observations of these two events and identify them as sympathetic filament eruptions. The first (F1) is a small active-region filament located near the outskirts of the streamer arcade. It underwent a nonradial eruption, initially moving in the interior of the streamer arcade and resulting in an over-and-out coronal mass ejection. The second filament (F2), a larger quiescent one far away from F1, was clearly disturbed during the F1 eruption. It then underwent a very slow eruption and finally disappeared completely and permanently. Because two belt-shaped diffuse dimmings formed along the footprints of the streamer arcade in the first eruption and persisted throughout the complete disappearance of F2, the eruption series are interpreted as sympathetic: the simple expansion of the common streamer arcade forced by the F1 eruption weakened magnetic flux overlying F2 and thus led to its slow eruption, with the dimming formation indicating their physical connection. Our observations suggest that multiple-arcade bipolar helmet-streamer configurations are appropriate to producing sympathetic eruptions. Combined with the recent observations of unipolar-streamer sympathetic events, it appears that a multiple-arcade unipolar or bipolar helmet streamer can serve as a common magnetic configuration for sympathetic eruptions.

Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

Science.gov (United States)

Fuente Mora, Cristina; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

2015-11-01

What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic

Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

Directory of Open Access Journals (Sweden)

Lechin F

2010-09-01

predominance of overwhelming adrenal sympathetic activity over neural sympathetic activity. This combined central and autonomic nervous system profile contrasts with that registered in patients affected by hyperinsulinism, hypoglycemia, and bulimia syndrome which depends on the absolute predominance of neural sympathetic activity.Keywords: anorexia nervosa, adrenal sympathetic activity, adrenaline, noradrenaline, eating disorders

Epicardial distribution of ST segment and T wave changes produced by stimulation of intrathoracic ganglia or cardiopulmonary nerves in dogs.

Science.gov (United States)

Savard, P; Cardinal, R; Nadeau, R A; Armour, J A

1991-06-01

Sixty-three ventricular epicardial electrograms were recorded simultaneously in 8 atropinized dogs during stimulation of acutely decentralized intrathoracic autonomic ganglia or cardiopulmonary nerves. Three variables were measured: (1) isochronal maps representing the epicardial activation sequence, (2) maps depicting changes in areas under the QRS complex and T wave (regional inhomogeneity of repolarization), and (3) local and total QT intervals. Neural stimulations did not alter the activation sequence but induced changes in the magnitude and polarity of the ST segments and T waves as well as in QRST areas. Stimulation of the same neural structure in different dogs induced electrical changes with different amplitudes and in different regions of the ventricles, except for the ventral lateral cardiopulmonary nerve which usually affected the dorsal wall of the left ventricle. Greatest changes occurred when the right recurrent, left intermediate medial, left caudal pole, left ventral lateral cardiopulmonary nerves and stellate ganglia were stimulated. Local QT durations either decreased or did not change, whereas total QT duration as measured using a root-mean-square signal did not change, indicating the regional nature of repolarization changes. Taken together, these data indicate that intrathoracic efferent sympathetic neurons can induce regional inhomogeneity of repolarization without prolonging the total QT interval.

Sympatho-renal axis in chronic disease.

Science.gov (United States)

Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

2011-12-01

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

International Nuclear Information System (INIS)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-01-01

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

Energy Technology Data Exchange (ETDEWEB)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-02-15

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation

DEFF Research Database (Denmark)

Lundby, Lilli; Møller, Arne; Buntzen, Steen

2011-01-01

This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence.......This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence....

A comparison between 133Xenon washout technique and Laser Doppler flowmetry in the measurement of local vasoconstrictor effects on the microcirculation in subcutaneous tissue and skin

DEFF Research Database (Denmark)

Kastrup, J; Bülow, J; Lassen, N A

1987-01-01

Changes in skin blood flow measured by Laser Doppler flowmetry and changes in subcutaneous blood flow measured by 133Xenon washout technique were compared during activation of the local sympathetic mediated veno-arteriolar vasoconstrictor reflex by lowering the area of investigation below heart...... forearm, and on the calf with preserved sympathetic nerve supply. The Laser Doppler method registered a 23% reduction in skin blood flow during lowering of the extremities independently of the sympathetic nerve supply to the skin. The 133Xenon method recorded a 44% decrease in blood flow in innervated...... level. The measurements were performed in tissue with and without sympathetic innervation. In five subjects, who all had been cervically sympathectomized for manual hyperhidrosis, the Laser Doppler and 133Xenon blood flow measurements were performed simultaneously on the sympathetically denervated...

The biophysics of renal sympathetic denervation using radiofrequency energy.

Science.gov (United States)

Patel, Hitesh C; Dhillon, Paramdeep S; Mahfoud, Felix; Lindsay, Alistair C; Hayward, Carl; Ernst, Sabine; Lyon, Alexander R; Rosen, Stuart D; di Mario, Carlo

2014-05-01

Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

International Nuclear Information System (INIS)

DiCicco-Bloom, E.; Black, I.B.

1988-01-01

While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [ 3 H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [ 3 H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

Nerve growth factor promotes human hemopoietic colony growth and differentiation

International Nuclear Information System (INIS)

Matsuda, H.; Coughlin, M.D.; Bienenstock, J.; Denburg, J.A.

1988-01-01

Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been clones. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. These experiments indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by 125 I-polyclonal and monoclonal antibodies to NGF. The authors conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, they postulate that NGF plays an important biological role in a variety of repair processes

Central and peripheral nervous systems: master controllers in cancer metastasis.

Science.gov (United States)

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Concurrent sympathetic activation and vagal withdrawal in hyperthyroidism: Evidence from detrended fluctuation analysis of heart rate variability

Science.gov (United States)

Chen, Jin-Long; Shiau, Yuo-Hsien; Tseng, Yin-Jiun; Chiu, Hung-Wen; Hsiao, Tzu-Chien; Wessel, Niels; Kurths, Jürgen; Chu, Woei-Chyn

2010-05-01

Despite many previous studies on the association between hyperthyroidism and the hyperadrenergic state, controversies still exist. Detrended fluctuation analysis (DFA) is a well recognized method in the nonlinear analysis of heart rate variability (HRV), and it has physiological significance related to the autonomic nervous system. In particular, an increased short-term scaling exponent α1 calculated from DFA is associated with both increased sympathetic activity and decreased vagal activity. No study has investigated the DFA of HRV in hyperthyroidism. This study was designed to assess the sympathovagal balance in hyperthyroidism. We performed the DFA along with the linear analysis of HRV in 36 hyperthyroid Graves’ disease patients (32 females and 4 males; age 30 ± 1 years, means ± SE) and 36 normal controls matched by sex, age and body mass index. Compared with the normal controls, the hyperthyroid patients revealed a significant increase ( Phyperthyroid 1.28±0.04 versus control 0.91±0.02), long-term scaling exponent α2 (1.05±0.02 versus 0.90±0.01), overall scaling exponent α (1.11±0.02 versus 0.89±0.01), low frequency power in normalized units (LF%) and the ratio of low frequency power to high frequency power (LF/HF); and a significant decrease ( Phyperthyroidism is characterized by concurrent sympathetic activation and vagal withdrawal. This sympathovagal imbalance state in hyperthyroidism helps to explain the higher prevalence of atrial fibrillation and exercise intolerance among hyperthyroid patients.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

Science.gov (United States)

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

Science.gov (United States)

Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

2015-04-16

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

Transient receptor potential A1 channel contributes to activation of the muscle reflex.

Science.gov (United States)

Koba, Satoshi; Hayes, Shawn G; Sinoway, Lawrence I

2011-01-01

This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.

Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress.

Science.gov (United States)

El Sayed, Khadigeh; Macefield, Vaughan G; Hissen, Sarah L; Joyner, Michael J; Taylor, Chloe E

2016-12-15

Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders. Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex-mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA-driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task. Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post-exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s -1 ) compared with positive responders (0.4 ± 0.1 mmHg s -1 ; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across

Vibration sense and sympathetic vasoconstrictor activity in patients with occlusive arterial disease

DEFF Research Database (Denmark)

Bjerre-Jepsen, K; Henriksen, O; Parm, Martin Lehnsbo

1983-01-01

function was studied by the capability of the local sympathetic venoarteriolar reflex (Henriksen 1977) elicited by lowering the leg to induce an arteriolar constriction in subcutaneous tissue at the ankle level. Blood flow was measured by the local isotope washout technique. In only five patients with loss...

Sympathetic Activity, Assessed by Power Spectral Analysis of Heart Rate Variability, in White-Coat, Masked and Sustained Hypertension Versus True Normotension

Czech Academy of Sciences Publication Activity Database

Fagard, R.H.; Stolarz, K.; Kuznetsova, T.; Seidlerová, J.; Tikhonoff, V.; Grodzicki, T.; Nikitin, Y.; Filipovský, J.; Peleška, Jan; Casiglia, E.; Thijs, L.; Staessen, J.A.; Kawecka-Jaszcz, K.

2007-01-01

Roč. 25, č. 11 (2007), s. 2280-2285 ISSN 0263-6352 Institutional research plan: CEZ:AV0Z10300504 Keywords : heart rate variability * masked hypertension * power spectral analysis * sympathetic activity * white-coat hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.364, year: 2007

Marital conflict and children's externalizing behavior: interactions between parasympathetic and sympathetic nervous system activity

National Research Council Canada - National Science Library

El-Sheikh, Mona; Beauchaine, Theodore P; Moore, Ginger A

2009-01-01

"Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS...

The Influence of Prolonged Acetylsalicylic Acid Supplementation-Induced Gastritis on the Neurochemistry of the Sympathetic Neurons Supplying Prepyloric Region of the Porcine Stomach.

Directory of Open Access Journals (Sweden)

Katarzyna Palus

Full Text Available This experiment was designed to establish the localization and neurochemical phenotyping of sympathetic neurons supplying prepyloric area of the porcine stomach in a physiological state and during acetylsalicylic acid (ASA induced gastritis. In order to localize the sympathetic perikarya the stomachs of both control and acetylsalicylic acid treated (ASA group animals were injected with neuronal retrograde tracer Fast Blue (FB. Seven days post FB injection, animals were divided into a control and ASA supplementation group. The ASA group was given 100 mg/kg of b.w. ASA orally for 21 days. On the 28th day all pigs were euthanized with gradual overdose of anesthetic. Then fourteen-micrometer-thick cryostat sections were processed for routine double-labeling immunofluorescence, using primary antisera directed towards tyrosine hydroxylase (TH, dopamine β-hydroxylase (DβH, neuropeptide Y (NPY, galanin (GAL, neuronal nitric oxide synthase (nNOS, leu 5-enkephalin (LENK, cocaine- and amphetamine- regulated transcript peptide (CART, calcitonin gene-related peptide (CGRP, substance P (SP and vasoactive intestinal peptide (VIP. The data obtained in this study indicate that postganglionic sympathetic nerve fibers supplying prepyloric area of the porcine stomach originate from the coeliac-cranial mesenteric ganglion complex (CCMG. In control animals, the FB-labelled neurons expressed TH (94.85 ± 1.01%, DβH (97.10 ± 0.97%, NPY (46.88 ± 2.53% and GAL (8.40 ± 0.53%. In ASA group, TH- and DβH- positive nerve cells were reduced (85.78 ± 2.65% and 88.82 ± 1.63% respectively. Moreover, ASA- induced gastritis resulted in increased expression of NPY (76.59 ± 3.02% and GAL (26.45 ± 2.75% as well as the novo-synthesis of nNOS (6.13 ± 1.11% and LENK (4.77 ± 0.42% in traced CCMG neurons. Additionally, a network of CART-, CGRP-, SP-, VIP-, LENK-, nNOS- immunoreactive (IR nerve fibers encircling the FB-positive perikarya were observed in both intact and ASA

Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice

Directory of Open Access Journals (Sweden)

Zhifang Zheng

2017-01-01

Full Text Available Previous studies focused on the effects of sympathetic denervation with 6-hydroxydopamine (6-OHDA on nondiabetic wounds, but the effects of 6-OHDA on diabetic wounds have not been previously reported. In this study, treated mice received intraperitoneal 6-OHDA, and control mice received intraperitoneal injections of normal saline. Full-thickness wounds were established on the backs of mice. The wounds were sectioned (four mice per group for analysis at 2, 5, 7, 10, 14, 17, and 21 days after injury. The wound areas in the control group were larger than those in the treatment group. Histological scores for epidermal and dermal regeneration were reduced in the 6-OHDA-treated group on day 21. The mast cells (MCs in each field decreased after sympathectomy on days 17 and 21. The expression levels of norepinephrine, epidermal growth factor (EGF, interleukin-1 beta, NG2 proteoglycan, and desmin in the treatment group were less than those in the control group. In conclusion, 6-OHDA delays reepithelialization during wound healing in diabetic mice by decreasing EGF, but increases wound contraction by reducing IL-1β levels and the number of MCs. Besides, 6-OHDA led to reduced pericyte proliferation in diabetic wounds, which might explain the vascular dysfunction after sympathetic nerve loss in diabetic wounds.

Vagus nerve stimulation for epilepsy activates the vocal folds maximally at therapeutic levels.

NARCIS (Netherlands)

Ardesch, J.J.; Sikken, J.R.; Veltink, Petrus H.; van der Aa, H.E.; Hageman, G.; Buschman, H.P.J.

Purpose Vagus nerve stimulation (VNS) for medically refractory epilepsy can give hoarseness due to stimulation of the recurrent laryngeal nerve. For a group of VNS-therapy users this side-effect interferes severely with their daily activities. Our goal was to investigate the severity of

Superoxide Anions and NO in the Paraventricular Nucleus Modulate the Cardiac Sympathetic Afferent Reflex in Obese Rats

Directory of Open Access Journals (Sweden)

Qing-Bo Lu

2017-12-01

Full Text Available This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2− and nitric oxide (NO system of the paraventricular nucleus (PVN regulates the cardiac sympathetic afferent reflex (CSAR contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA and the mean arterial pressure (MAP responses to the epicardial application of capsaicin (CAP in anaesthetized rats. In obese rats with hypertension (OH group or without hypertension (OB group, the levels of PVN O2−, angiotensinII (Ang II, Ang II type 1 receptor (AT1R, and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were elevated, whereas neural NO synthase (nNOS and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD and the NO donor sodium nitroprusside (SNP, and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC and the nNOS inhibitor N(ω-propyl-l-arginine hydrochloride (PLA; conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2− and NO system that modulates CSAR and promotes sympathoexcitation.

Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41).

Science.gov (United States)

Kimura, Ikuo; Inoue, Daisuke; Maeda, Takeshi; Hara, Takafumi; Ichimura, Atsuhiko; Miyauchi, Satoshi; Kobayashi, Makio; Hirasawa, Akira; Tsujimoto, Gozoh

2011-05-10

The maintenance of energy homeostasis is essential for life, and its dysregulation leads to a variety of metabolic disorders. Under a fed condition, mammals use glucose as the main metabolic fuel, and short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber also contribute a significant proportion of daily energy requirement. Under ketogenic conditions such as starvation and diabetes, ketone bodies produced in the liver from fatty acids are used as the main energy sources. To balance energy intake, dietary excess and starvation trigger an increase or a decrease in energy expenditure, respectively, by regulating the activity of the sympathetic nervous system (SNS). The regulation of metabolic homeostasis by glucose is well recognized; however, the roles of SCFAs and ketone bodies in maintaining energy balance remain unclear. Here, we show that SCFAs and ketone bodies directly regulate SNS activity via GPR41, a Gi/o protein-coupled receptor for SCFAs, at the level of the sympathetic ganglion. GPR41 was most abundantly expressed in sympathetic ganglia in mouse and humans. SCFA propionate promoted sympathetic outflow via GPR41. On the other hand, a ketone body, β-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS activity by antagonizing GPR41. Pharmacological and siRNA experiments indicated that GPR41-mediated activation of sympathetic neurons involves Gβγ-PLCβ-MAPK signaling. Sympathetic regulation by SCFAs and ketone bodies correlated well with their respective effects on energy consumption. These findings establish that SCFAs and ketone bodies directly regulate GPR41-mediated SNS activity and thereby control body energy expenditure in maintaining metabolic homeostasis.

Diabetic cardiac autonomic dysfunction. Parasympathetic versus sympathetic

International Nuclear Information System (INIS)

Uehara, Akihiko; Kurata, Chinori; Sugi, Toshihiko; Mikami, Tadashi; Shouda, Sakae

1999-01-01

Diabetic cardiac autonomic dysfunction often causes lethal arrhythmia and sudden cardiac death. 123 I-Metaiodobenzylguanidine (MIBG) can evaluate cardiac sympathetic dysfunction, and analysis of heart rate variability (HRV) can reflect cardiac parasympathetic activity. We examined whether cardiac parasympathetic dysfunction assessed by HRV may correlate with sympathetic dysfunction assessed by MIBG in diabetic patients. In 24-hour electrocardiography, we analyzed 4 HRV parameters: high-frequency power (HF), HF in the early morning (EMHF), rMSSD and pNN50. MIBG planar images and SPECT were obtained 15 minutes (early) and 150 minutes (late) after injection and the heart washout rate was calculated. The defect score in 9 left ventricular regions was scored on a 4 point scale (0=normal - 3=severe defect). In 20 selected diabetic patients without congestive heart failure, coronary artery disease and renal failure, parasympathetic HRV parameters had a negative correlation with the sum of defect scores (DS) in the late images (R=-0.47 to -0.59, p<0.05) and some parameters had a negative correlation with the washout rate (R=-0.50 to -0.55, p<0.05). In a total of 64 diabetic patients also, these parameters had a negative correlation with late DS (R=-0.28 to -0.35, p<0.05) and early DS (R=-0.27 to -0.32, p<0.05). The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one. (author)

Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury.

Science.gov (United States)

Wang, Ruihao; Hösl, Katharina M; Ammon, Fabian; Markus, Jörg; Koehn, Julia; Roy, Sankanika; Liu, Mao; de Rojas Leal, Carmen; Muresanu, Dafin; Flanagan, Steven R; Hilz, Max J

2018-06-01

After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. In 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Using a forehead reflectance pulse oximeter to detect changes in sympathetic tone.

Science.gov (United States)

Wendelken, Suzanne M; McGrath, Susan P; Akay, Metin; Blike, George T

2004-01-01

The extreme conditions of combat and multi-casualty rescue often make field triage difficult and put the medic or first responder at risk. In an effort to improve field triage, we have developed an automated remote triage system called ARTEMIS (automated remote triage and emergency management information system) for use in the battlefield or disaster zone. Common to field injuries is a sudden change in arterial pressure resulting from massive blood loss or shock. In effort to stabilize the arterial pressure, the sympathetic system is strongly activated and sympathetic tone is increased. This preliminary research seeks to empirically demonstrate that a forehead reflectance pulse oximeter is a viable sensor for detecting sudden changes in sympathetic tone. We performed the classic supine-standing experiment and collected the raw waveform, the photoplethysmogram (PPG), continuously using a forehead reflectance pulse oximeter. The resulting waveform was processed in Matlab using various spectral analysis techniques (FFT and AR). Our preliminary results show that a relative ratio analysis (low frequency power/high frequency power) for both the raw PPG signal and its derived pulse statistics (height, beat-to-beat interval) is a useful technique for detecting change in sympathetic tone resulting from positional change.

Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

Science.gov (United States)

Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

2018-04-01

Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

The clinical value of cardiac sympathetic imaging in heart failure

DEFF Research Database (Denmark)

Christensen, Thomas Emil; Kjaer, Andreas; Hasbak, Philip

2014-01-01

The autonomic nervous system plays an important role in the pathology of heart failure. The single-photon emission computed tomography tracer iodine-123-metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of the predominant neurotransmitter of the sympathetic nervous...

EFFECT OF LIVER DENERVATION ON GLUCOSE-PRODUCTION DURING RUNNING IN GUINEA-PIGS

NARCIS (Netherlands)

WIERSMA, MML; VISSING, J; MIKINES, KJ; STEFFENS, AB; GALBO, H

Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

Science.gov (United States)

Butler, C; Watson-Wright, W M; Wilkinson, M; Johnstone, D E; Armour, J A

1988-03-01

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long

Laser-activated protein solder for peripheral nerve repair

Science.gov (United States)

Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

1995-05-01

A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

Science.gov (United States)

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy

DEFF Research Database (Denmark)

Nielsen, F S; Hansen, H P; Jacobsen, P

1999-01-01

AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity...... (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly...... constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably...

Autonomic control of body temperature and blood pressure: influences of female sex hormones.

Science.gov (United States)

Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

2017-06-01

Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats.

Science.gov (United States)

Barella, Luiz F; Miranda, Rosiane A; Franco, Claudinéia C S; Alves, Vander S; Malta, Ananda; Ribeiro, Tatiane A S; Gravena, Clarice; Mathias, Paulo C F; de Oliveira, Júlio C

2015-01-01

What is the central question of this study? Different nerve contributes periods of life are known for their differential sensitivity to interventions, and increased parasympathetic activity affects the development and maintenance of obesity. Thus, we evaluated the involvement of the vagus nerve by performing a vagotomy in young or adult rats that were offered an obesogenic high-fat diet. What is the main finding and its importance? Although the accumulation of adipose tissue decreased in both younger and older groups, the younger rats showed a greater response to the effects of vagotomy in general. In addition to the important role of the parasympathetic activity, we suggest that the vagus nerve contributes to the condition of obesity. Obesity has become a global problem, and this condition develops primarily because of an imbalance between energy intake and expenditure. The high complexity involved in the regulation of energy metabolism results from several factors besides endocrine factors. It has been suggested that obesity could be caused by an imbalance in the autonomous nervous system, which could lead to a condition of high parasympathetic activity in counterpart to low sympathetic tonus. High-fat (HF) diets have been used to induce obesity in experimental animals, and their use in animals leads to insulin resistance, hyperinsulinaemia and high parasympathetic activity, among other disorders. The aim of this work was to evaluate the effects of a vagotomy performed at the initiation of a HF diet at two different stages of life, weaning and adulthood. The vagotomy reduced parasympathetic activity (-32 and -51% in normal fat-fed rats and -43 and -55% in HF diet-fed rats; P fat depots (-17 and -33%, only in HF diet-fed rats; P fat diet-fed rats exhibited fasting hyperinsulinaemia (fivefold higher in young rats and threefold higher in older rats; P diet-fed groups was not altered in the vagotomized rats. We suggest that the vagus nerve, in addition to the

Laser-activated protein bands for peripheral nerve repair

Science.gov (United States)

Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

1996-01-01

A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

Patterns of Sympathetic Responses Induced by Different Stress Tasks

Science.gov (United States)

Fechir, M; Schlereth, T; Purat, T; Kritzmann, S; Geber, C; Eberle, T; Gamer, M; Birklein, F

2008-01-01

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction. Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research. PMID:19018304

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

Science.gov (United States)

Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

2015-07-01

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

DEFF Research Database (Denmark)

Vagn Nielsen, H; Hasselström, K; Feldt-Rasmussen, U

1987-01-01

vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater...... than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied.......02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment....

Effects of short-term carvedilol on the cardiac sympathetic activity assessed by {sup 123}I-MIBG scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Miranda, Sandra Marina Ribeiro de; Mesquita, Evandro Tinoco; Freire, Fabiano de Lima; Ribeiro, Mario Luiz; Nobrega, Antonio Claudio Lucas da; Mesquita, Claudio Tinoco, E-mail: sandramarina@cardiol.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Azevedo, Jader Cunha; Barbirato, Gustavo Borges; Coimbra, Alexandro [Hospital Pro-Cardiaco, Rio de Janeiro, RJ (Brazil); Dohmann, Hans Fernando da Rocha [Centro de Ensino e Pesquisa do Pro-Cardiaco (PROCEP), Rio de Janeiro, RJ (Brazil)

2010-03-15

Background: autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine ({sup 123}I-MIBG) scintigraphy imaging of the heart. Objective: to evaluate the cardiac sympathetic activity through {sup 123}I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45%. Patients and methods: sixteen patients, aged 56.3 +- 12.6 years (11 males), with a mean LVEF of 28% +- 8% and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with {sup 123}I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. Results: patients' functional class showed improvement: before the treatment, 50% of the patients were FC II and 50% were FC III. After 3 months, 7 patients were FC I (43.8%) and 9 were FC II (56.2%), (rho = 0.0001). The mean LVEF assessed by RIV increased from 29% to 33% (rho = 0.017). There was no significant variation in cardiac adrenergic activity assessed by {sup 123}I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. Conclusion: the short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by {sup 123}I-MIBG scintigraphy, as well as the measurement of circulating catecholamines. (author)

Facial nerve activity disrupts psychomotor rhythms in the forehead microvasculature.

Science.gov (United States)

Drummond, Peter D; O'Brien, Geraldine

2011-10-28

Forehead blood flow was monitored in seven participants with a unilateral facial nerve lesion during relaxation, respiratory biofeedback and a sad documentary. Vascular waves at 0.1Hz strengthened during respiratory biofeedback, in tune with breathing cycles that also averaged 0.1Hz. In addition, a psychomotor rhythm at 0.15Hz was more prominent in vascular waveforms on the denervated than intact side of the forehead, both before and during relaxation and the sad documentary. These findings suggest that parasympathetic activity in the facial nerve interferes with the psychomotor rhythm in the forehead microvasculature. Copyright © 2011 Elsevier B.V. All rights reserved.

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

Science.gov (United States)

Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.

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Kox, Matthijs; van Eijk, Lucas T; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C G J; van der Hoeven, Johannes G; Pickkers, Peter

2014-05-20

Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.

Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

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Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

2016-12-14

Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

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Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

2017-08-01

Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training.

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Rebecca L Scalzo

Full Text Available The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21 were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11. The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE, but was increased during hypoxia mediated sympathetic activation (368±135; this response was abrogated (P = 0.035 with clonidine (269±93. Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21. Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5 was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT. SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046 but did not affect FNDC5 (P = 0.79. Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045 and increased in females (139±14 vs. 170±18. Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.

Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

International Nuclear Information System (INIS)

Imamura, Yoshihiro; Fukuyama, Takaya

1997-01-01

Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

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Joana Beatriz Sousa

Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

Inflammation in CRPS: role of the sympathetic supply.

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Schlereth, Tanja; Drummond, Peter D; Birklein, Frank

2014-05-01

Acute Complex Regional Pain Syndrome (CRPS) is associated with signs of inflammation such as increased skin temperature, oedema, skin colour changes and pain. Pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-1beta, IL-6) are up-regulated, whereas anti-inflammatory cytokines (IL-4, IL-10) are diminished. Adaptive immunity seems to be involved in CRPS pathophysiology as many patients have autoantibodies directed against β2 adrenergic and muscarinic-2 receptors. In an animal tibial fracture model changes in the innate immune response such as up-regulation of keratinocytes are also found. Additionally, CRPS is accompanied by increased neurogenic inflammation which depends mainly on neuropeptides such as CGRP and Substance P. Besides inflammatory signs, sympathetic nervous system involvement in CRPS results in cool skin, increased sweating and sympathetically-maintained pain. The norepinephrine level is lower in the CRPS-affected than contralateral limb, but sympathetic sprouting and up-regulation of alpha-adrenoceptors may result in an adrenergic supersensitivity. The sympathetic nervous system and inflammation interact: norepinephrine influences the immune system and the production of cytokines. There is substantial evidence that this interaction contributes to the pathophysiology and clinical presentation of CRPS, but this interaction is not straightforward. How inflammation in CRPS might be exaggerated by sympathetic transmitters requires further elucidation. Copyright © 2014 Elsevier B.V. All rights reserved.

Traditional Chinese herbal formula relieves snoring by modulating activities of upper airway related nerves in aged rats

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Chung KT

2018-05-01

Full Text Available Kou-Toung Chung,* Chih-Hsiang Hsu,* Ching-Lung Lin, Sheue-Er Wang, Chung-Hsin WuDepartment of Life Science, National Taiwan Normal University, Taipei, Taiwan*These authors contributed equally to this workAim: The present study investigated whether intraperitoneal treatment with the herbal formula B210 ([B210]; a herbal composition of Gastrodia elata and Cinnamomum cassia can reduce snoring in aged rats. Also, we studied possible neural mechanisms involved in B210 treatment and subsequent reduced snoring in rats.Methods and result: We compared pressure and frequency of snoring, activities of phrenic nerve (PNA, activities of recurrent laryngeal nerve (RLNA and activities of hypoglossal nerve (HNA, inspiratory time (TI and expiratory time (TE of PNA, and pre-inspiratory time (Pre-TI of HNA in aged rats between sham and B210 treatment groups (30 mg/mL dissolved in DMSO. We found that aged rats that received B210 treatment had significantly reduced pressure and frequency of snoring than rats who received sham treatment. Also, we observed that aged rats that received B210 treatment had significantly increased PNA, RLNA, and HNA, extended TI and TE of PNA, and prolonged Pre-TI of HNA compared to rats that received sham treatment. In other words, B210 treatment may relieve snoring through modulating activities and breathing time of upper airway related nerves in aged rats.Conclusion: We suggested that the B210 might be a potential herbal formula for snoring remission.Keywords: Chinese herbal medicine, snoring remission, upper airway, phrenic nerve, recurrent laryngeal nerve, hypoglossal nerve

Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats.

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Zhou, Hong; Sun, Hai-jian; Chang, Jin-rui; Ding, Lei; Gao, Qing; Tang, Chao-shu; Zhu, Guo-qing; Zhou, Ye-bo

2014-10-01

Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or γ-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats. © 2014 by the Society for Experimental Biology and Medicine.

A comparison between 133Xenon washout technique and Laser Doppler flowmetry in the measurement of local vasoconstrictor effects on the microcirculation in subcutaneous tissue and skin

International Nuclear Information System (INIS)

Kastrup, J.; Buelow, J.; Lassen, N.A.

1987-01-01

Changes in skin blood flow measured by Laser Doppler flowmetry and changes in subcutaneous blood flow measured by 133 Xenon washout technique were compared during activation of the local sympathetic mediated veno-arteriolar vaso-constrictor reflex by lowering the area of investigation below heart level. The measurements were performed in tissue with and without sympathetic innervation. In five subjects, who all had been cervically sympathectomized for manual hyperhidrosis, the Laser Doppler and 133 Xenon blood flow measurements were performed simultaneously on the sympathetically denervated forearm, and on the calf with preserved sympathetic nerve supply. The Laser Doppler method registered a 23% reduction in skin blood flow during lowering of the extremities independently of the sympathetic nerve supply to the skin. The 133 Xenon method recorded a 44% decrease in blood flow in innervated and unchanged blood flow in denervated subcutaneous tissue during lowering of the extremities. Our results indicate that the Laser Doppler method and 133 Xenon method are not comparable, and that the Laser Doppler method is not useful in measuring local sympathetic mediated blood flow changes. (author)

Comparison between /sup 133/Xenon washout technique and Laser Doppler flowmetry in the measurement of local vasoconstrictor effects on the microcirculation in subcutaneous tissue and skin

Energy Technology Data Exchange (ETDEWEB)

Kastrup, J.; Buelow, J.; Lassen, N.A.

1987-10-01

Changes in skin blood flow measured by Laser Doppler flowmetry and changes in subcutaneous blood flow measured by /sup 133/Xenon washout technique were compared during activation of the local sympathetic mediated veno-arteriolar vaso-constrictor reflex by lowering the area of investigation below heart level. The measurements were performed in tissue with and without sympathetic innervation. In five subjects, who all had been cervically sympathectomized for manual hyperhidrosis, the Laser Doppler and /sup 133/Xenon blood flow measurements were performed simultaneously on the sympathetically denervated forearm, and on the calf with preserved sympathetic nerve supply. The Laser Doppler method registered a 23% reduction in skin blood flow during lowering of the extremities independently of the sympathetic nerve supply to the skin. The /sup 133/Xenon method recorded a 44% decrease in blood flow in innervated and unchanged blood flow in denervated subcutaneous tissue during lowering of the extremities. Our results indicate that the Laser Doppler method and /sup 133/Xenon method are not comparable, and that the Laser Doppler method is not useful in measuring local sympathetic mediated blood flow changes.

Functionality of the baroreceptor nerves in heart rate regulation

DEFF Research Database (Denmark)

Ottesen, Johnny T.; Olufsen, Mette

2011-01-01

are a consequence of the memory encapsulated by the models, and the nonlinearity gives rise to sigmoidal response curves. The nonlinear afferent baroreceptor models are coupled with an effector model, and the coupled model has been used to predict baroreceptor feedback regulation of heart rate during postural...... change from sitting to standing and during head-up tilt. The efferent model couples the afferent nerve paths to the sympathetic and parasympathetic outflow, and subsequently predicts the build up of an action potential at the sinus knot of the heart. In this paper, we analyze the nonlinear afferent model...... and show that the coupled model is able to predict heart rate regulation using blood pressure data as an input...

Degenerative Nerve Diseases

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Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

An Acute Bout of a Controlled Breathing Frequency Lowers Sympathetic Neural Outflow but not Blood Pressure in Healthy Normotensive Subjects

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MCCLAIN, SHANNON L.; BROOKS, ALEXA M.; JARVIS, SARA S.

2017-01-01

Controlled or paced breathing is often used as a stress reduction technique but the impact on blood pressure (BP) and sympathetic outflow have not been consistently reported. The purpose of this study was to determine whether a controlled breathing (12 breaths/min, CB) rate would be similar to an individual’s spontaneous breathing (SB) rate. Secondly, would a CB rate of 12 breaths/min alter heart rate (HR), BP, and indices of muscle sympathetic nerve activity (MSNA). Twenty-one subjects (10 women, 11 men) performed two trials: SB, where the subject chose a comfortable breathing rate; and CB, where the subject breathed at a pace of 12 breaths/min. Each trial was 6 min during which respiratory waveforms, HR, BP (systolic, SBP; diastolic, DBP), and MSNA were recorded. During CB, the 6 min average breathing frequency (14±4 vs 12±1 breaths/min, P<0.05 for SB and CB, respectively), MSNA burst frequency (18±12 vs 14±10 bursts/min, P<0.01) and MSNA burst incidence (28±19 vs 21± 6 bursts/100 heart beats, P<0.01) were significantly lower than during SB. HR (66±9 vs 67±9 beats/min, P<0.05) was higher during CB. SBP (120±13 vs 121±15 mmHg, P=0.741), DBP (56±8 vs 57±9 mmHg, P=0.768), and MSNA total activity (166±94 vs 145±102 a.u./min, P=0.145) were not different between the breathing conditions. In conclusion, an acute reduction in breathing frequency such as that observed during CB elicited a decrease in indices of MSNA (burst frequency and incidence) with no change in BP. PMID:28344733

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

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He, Baoming; Yu, Liang; Li, Suping; Xu, Fei; Yang, Lili; Ma, Shuai; Guo, Yi

2018-04-01

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of

Renal sympathetic denervation: MDCT evaluation of the renal arteries.

LENUS (Irish Health Repository)

Hutchinson, Barry D

2013-08-01

Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

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Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

2008-11-01

Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

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Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

2013-11-01

We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP amplitude are less associated with spontaneous activity, implying that needle EMG examination should be recommended for the detection of

High-Frequency Electrical Modulation of the Superior Ovarian Nerve as a Treatment of Polycystic Ovary Syndrome in the Rat.

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Pikov, Victor; Sridhar, Arun; Lara, Hernan E

2018-01-01

The polycystic ovary syndrome (PCOS) is the most prevalent ovarian pathology in women, with excessive sympathetic activity in the superior ovarian nerve (SON) playing an important role in inducing the PCOS symptoms in the rats and humans. Our previous studies have shown that surgical transection of the SON can reverse the disease progression, prompting us to explore the effect of the kilohertz frequency alternating current (KHFAC) modulation as a method of reversible non-surgical suppression of the nerve activity in the rodent model of PCOS. 56 animals were randomly allocated to three groups: the Control group ( n = 18), the PCOS group ( n = 15), and the PCOS + KHFAC group ( n = 23). The physiological, anatomical, and biochemical parameters of ovarian function were evaluated during the progression of the experimentally-induced PCOS and during long-term KHFAC modulation applied for 2-3 weeks. The KHFAC modulation has been able to reverse the pathological changes in assessed PCOS parameters, namely the irregular or absent estrous cycling, formation of ovarian cysts, reduction in the number of corpora lutea, and ovarian norepinephrine concentration. The fertility capacity was similar in the PCOS and the PCOS + KHFAC groups, indicating the safety of KHFAC modulation approach. In summary, these results suggest that the KHFAC modulation approach of suppressing the SON activity could become a useful treatment modality for PCOS and potentially other pathological ovarian conditions.

High-Frequency Electrical Modulation of the Superior Ovarian Nerve as a Treatment of Polycystic Ovary Syndrome in the Rat

Directory of Open Access Journals (Sweden)

Victor Pikov

2018-05-01

Full Text Available The polycystic ovary syndrome (PCOS is the most prevalent ovarian pathology in women, with excessive sympathetic activity in the superior ovarian nerve (SON playing an important role in inducing the PCOS symptoms in the rats and humans. Our previous studies have shown that surgical transection of the SON can reverse the disease progression, prompting us to explore the effect of the kilohertz frequency alternating current (KHFAC modulation as a method of reversible non-surgical suppression of the nerve activity in the rodent model of PCOS. 56 animals were randomly allocated to three groups: the Control group (n = 18, the PCOS group (n = 15, and the PCOS + KHFAC group (n = 23. The physiological, anatomical, and biochemical parameters of ovarian function were evaluated during the progression of the experimentally-induced PCOS and during long-term KHFAC modulation applied for 2–3 weeks. The KHFAC modulation has been able to reverse the pathological changes in assessed PCOS parameters, namely the irregular or absent estrous cycling, formation of ovarian cysts, reduction in the number of corpora lutea, and ovarian norepinephrine concentration. The fertility capacity was similar in the PCOS and the PCOS + KHFAC groups, indicating the safety of KHFAC modulation approach. In summary, these results suggest that the KHFAC modulation approach of suppressing the SON activity could become a useful treatment modality for PCOS and potentially other pathological ovarian conditions.

A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

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Jackson, Kristy L; Marques, Francine Z; Watson, Anna M D; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Morris, Brian J; Charchar, Fadi J; Davern, Pamela J; Head, Geoffrey A

2013-10-01

Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.

Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervation in one-year old male Japanese macaques.

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Wilmon F Grant

Full Text Available Our group recently demonstrated that maternal high-fat diet (HFD consumption is associated with non-alcoholic fatty liver disease, increased apoptosis, and changes in gluconeogenic gene expression and chromatin structure in fetal nonhuman primate (NHP liver. However, little is known about the long-term effects that a HFD has on hepatic nervous system development in offspring, a system that plays an important role in regulating hepatic metabolism. Utilizing immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber density, apoptosis, inflammation, and other autonomic components in the livers of fetal and one-year old Japanese macaques chronically exposed to a HFD. We found that HFD exposure in-utero and throughout the postnatal period (HFD/HFD, when compared to animals receiving a CTR diet for the same developmental period (CTR/CTR, is associated with a 1.7 fold decrease in periportal sympathetic innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5 fold increase in hepatic apoptosis in the livers of one-year old male animals. Additionally, we observed an increase in hepatic inflammation and a decrease in a key component of the cholinergic anti-inflammatory pathway in one-year old HFD/HFD offspring. Taken together, these findings reinforce the impact that continuous exposure to a HFD has in the development of long-term hepatic pathologies in offspring and highlights a potential neuroanatomical basis for hepatic metabolic dysfunction.

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

OpenAIRE

Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

2013-01-01

Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

The Effect of Sympathetic Antagonists on the Antidepressant Action ...

African Journals Online (AJOL)

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

Assessment of left ventricular ejection force and sympathetic skin response in normotensive and hypertensive subjects: A double-blind observational comparative case–control study

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Tarun Saxena

2016-09-01

Conclusion: Stage 1 hypertension is a stage of increased sympathetic activity, leading to increased LVEF and hypertension (resetting of baroreceptors; stage 2 hypertension is a stage of normal sympathetic activity, increased LVEF, increased SV, and hypertension (possibly a stage of shift of renal equilibrium curve/renal output curve and blood pressure to a newer level.

Impact of aging on cardiac sympathetic innervation measured by {sup 123}I-mIBG imaging in patients with systolic heart failure

Energy Technology Data Exchange (ETDEWEB)

Rengo, Giuseppe; Ferrara, Nicola [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Pagano, Gennaro; Formisano, Roberto; Komici, Klara; Petraglia, Laura; Parisi, Valentina; Femminella, Grazia Daniela; De Lucia, Claudio; Cannavo, Alessandro; Memmi, Alessia; Leosco, Dario [University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Vitale, Dino Franco [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); Paolillo, Stefania [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Attena, Emilio [Fatebenefratelli Hospital, Department of Cardiology, Naples (Italy); Pellegrino, Teresa [Institute of Biostructures and Bioimages of the National Council of Research, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy); Dellegrottaglie, Santo [Ospedale Medico-Chirurgico Accreditato Villa dei Fiori, Division of Cardiology, Acerra, Naples (Italy); Trimarco, Bruno; Filardi, Pasquale Perrone [Federico II University of Naples, Division of Cardiology, Department of Advanced Biomedical Sciences, Naples (Italy); Cuocolo, Alberto [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy)

2016-12-15

Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine ({sup 123}I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac {sup 123}I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by {sup 123}I-mIBG scintigraphy, in patients with HF. We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac {sup 123}I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by {sup 123}I-mIBG imaging. This finding suggests that cardiac {sup 123}I-mIBG uptake in patients with HF might be affected by patient age. (orig.)

Renal sympathetic denervation in hypertension.

Science.gov (United States)

Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

2011-11-01

Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

Short-Term Red Wine Consumption Promotes Differential Effects on Plasma Levels of High-Density Lipoprotein Cholesterol, Sympathetic Activity, and Endothelial Function in Hypercholesterolemic, Hypertensive, and Healthy Subjects

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Andrade, Ana CM; Cesena, Fernando HY; Consolim-Colombo, Fernanda M; Coimbra, Silmara R; Benjó, Alexandre M; Krieger, Eduardo M; da Luz, Protasio Lemos

2009-01-01

OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine. PMID:19488610

Sympatho-renal axis in chronic disease

OpenAIRE

Sobotka, Paul A.; Mahfoud, Felix; Schlaich, Markus P.; Hoppe, Uta C.; B?hm, Michael; Krum, Henry

2011-01-01

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney?s somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for d...

Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: plasma norepinephrine concentration, hepatic extraction, and renal release

DEFF Research Database (Denmark)

Ring-Larsen, H; Hesse, B; Henriksen, Jens Henrik Sahl

1982-01-01

as previously reported in healthy controls. The right kidney released NE into the systemic circulation. Renal venous plasma NE exceeded arterial concentration by 34% (p less than 0.01). It is concluded that sympathetic nervous activity is enhanced in patients with cirrhosis, and that this hyperactivity may...... in patients than controls (82 vs. 95 mm Hg, p less than 0.05) but did not change during the tilt. Plasma norepinephrine (NE) concentration was significantly higher in another eight patients with cirrhosis than in eight healthy controls (mean: 0.45 vs. 0.21 ng per ml in recumbency, p less than 0.02). Following...

Detailed comparative anatomy of the extrinsic cardiac nerve plexus and postnatal reorganization of the cardiac position and innervation in the great apes: orangutans, gorillas, and chimpanzees.

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Kawashima, Tomokazu; Sato, Fumi

2012-03-01

To speculate how the extrinsic cardiac nerve plexus (ECNP) evolves phyletically and ontogenetically within the primate lineage, we conducted a comparative anatomical study of the ECNP, including an imaging examination in the great apes using 20 sides from 11 bodies from three species and a range of postnatal stages from newborns to mature adults. Although the position of the middle cervical ganglion (MG) in the great apes tended to be relatively lower than that in humans, the morphology of the ECNP in adult great apes was almost consistent with that in adult humans but essentially different from that in the lesser apes or gibbons. Therefore, the well-argued anatomical question of when did the MG acquire communicating branches with the spinal cervical nerves and appear constantly in all sympathetic cardiac nerves during primate evolution is clearly considered to be after the great apes and gibbons split. Moreover, a horizontal four-chambered heart and a lifted cardiac apex with a relatively large volume in newborn great apes rapidly changed its position downward, as seen in humans during postnatal growth and was associated with a reduction in the hepatic volume by imaging diagnosis and gross anatomy. In addition, our observation using a range of postnatal stages exhibits that two sympathetic ganglia, the middle cervical and cervicothoracic ganglia, differed between the early and later postnatal stages. Copyright © 2011 Wiley Periodicals, Inc.

Sensory and sympathetic correlates of heat pain sensitization and habituation in men and women.

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Breimhorst, M; Hondrich, M; Rebhorn, C; May, A; Birklein, F

2012-10-01

Habituation and sensitization are important behavioural responses to repeated exposure to painful stimuli, but little is known about the factors determining sensory, affective and sympathetic habituation to repeated pain stimulation in men and women. Thirty volunteers (15 women) underwent a standardized heat pain paradigm spread over 8 consecutive days. At the beginning of the experiment, personality dimensions, coping strategies and pain catastrophizing thoughts were determined. Receiving a series of 10 blocks of six painful heat stimuli a day, participants rated pain intensity and unpleasantness. Skin conductance was recorded throughout the sessions. The results show similar habituation of both the sensory and affective dimensions of pain in men and women, although skin conductance did not undergo a significant decrease across the eight days. When focusing on single daily sessions, women showed pain sensitization but sympathetic habituation, while men showed pain sensitization but stable sympathetic activation. Our findings therefore indicate that the process of long-term habituation to painful heat stimuli is a common feature in both genders, whereas men and women might differently recruit their sympathetic nervous system for short-term pain processing. This study could potentially help to better evaluate gender-specific mechanisms in pain perception. © 2012 European Federation of International Association for the Study of Pain Chapters.

Higher exercise intensity delays postexercise recovery of impedance-derived cardiac sympathetic activity.

Science.gov (United States)

Michael, Scott; Jay, Ollie; Graham, Kenneth S; Davis, Glen M

2017-08-01

Systolic time intervals (STIs) provide noninvasive insights into cardiac sympathetic neural activity (cSNA). As the effect of exercise intensity on postexercise STI recovery is unclear, this study investigated the STI recovery profile after different exercise intensities. Eleven healthy males cycled for 8 min at 3 separate intensities: LOW (40%-45%), MOD (75%-80%), and HIGH (90%-95%) of heart-rate (HR) reserve. Bio-impedance cardiography was used to assess STIs - primarily pre-ejection period (PEP; inversely correlated with cSNA), as well as left ventricular ejection time (LVET) and PEP:LVET - during 10 min seated recovery immediately postexercise. Heart-rate variability (HRV), i.e., natural-logarithm of root mean square of successive differences (Ln-RMSSD), was calculated as an index of cardiac parasympathetic neural activity (cPNA). Higher preceding exercise intensity elicited a slower recovery of HR and Ln-RMSSD (p return to baseline by 10 min following any intensity (p ≤ 0.009). Recovery of STIs was also slower following higher intensity exercise (p ≤ 0.002). By 30 s postexercise, higher preceding intensity resulted in a lower PEP (98 ± 14 ms, 75 ± 6 ms, 66 ± 5 ms for LOW, MOD, and HIGH, respectively, p fashion. While exercise intensity must be considered, acute recovery may be a valuable period during which to concurrently monitor these noninvasive indices, to identify potentially abnormal cardiac autonomic responses.

Retrogradely Transported TrkA Endosomes Signal Locally within Dendrites to Maintain Sympathetic Neuron Synapses

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Kathryn M. Lehigh

2017-04-01

Full Text Available Sympathetic neurons require NGF from their target fields for survival, axonal target innervation, dendritic growth and formation, and maintenance of synaptic inputs from preganglionic neurons. Target-derived NGF signals are propagated retrogradely, from distal axons to somata of sympathetic neurons via TrkA signaling endosomes. We report that a subset of TrkA endosomes that are transported from distal axons to cell bodies translocate into dendrites, where they are signaling competent and move bidirectionally, in close proximity to synaptic protein clusters. Using a strategy for spatially confined inhibition of TrkA kinase activity, we found that distal-axon-derived TrkA signaling endosomes are necessary within sympathetic neuron dendrites for maintenance of synapses. Thus, TrkA signaling endosomes have unique functions in different cellular compartments. Moreover, target-derived NGF mediates circuit formation and synapse maintenance through TrkA endosome signaling within dendrites to promote aggregation of postsynaptic protein complexes.

Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice

DEFF Research Database (Denmark)

Moldovan, Mihai; Alvarez Herrero, Susana; Rosberg, Mette R.

2016-01-01

Excitability of regenerated fibers remains impaired due to changes in both passive cable properties and alterations in the voltage-dependent membrane function. These abnormalities were studied by mathematical modeling in human regenerated nerves and experimental studies in mice. In three adult male...... activity protocol triggered partial Wallerian degeneration in regenerated nerves but not in control nerves from age-matched mice. The current data suggest that the nodal voltage-gated ion channel machinery is restored in regenerated axons, although the electrical separation from the internodal compartment...... remains compromised. Due to the persistent increase in number of nodes, the increased activity-dependent Na+ influx could lead to hyperactivity of the Na+/K+ pump resulting in membrane hyperpolarization and neurotoxic energy insufficiency during strenuous activity....

Active patient decision making regarding nerve sparing during radical prostatectomy: a novel approach.