Primer on the Autonomic Nervous System

Front Cover PRIMER ON THE AUTONOMIC NERVOUS SYSTEM PRIMER ON THE AUTONOMIC NERVOUS SYSTEM Copyright Contents Contributors Preface Acknowledgments I - Introduction 1 - Evolution of the cardiovascular autonomic nervous system in vertebrates The autonomic nervous system in vertebrates Anatomy of the cardiovascular system in vertebrates Autonomic regulation of the heart Innervation of the systemic vasculature Autonomic regulation of the pulmonary circulation Cardiorespiratory integration and respiratory sinus arrythmia The evolution of adrenergic and muscarinic receptors Cardiovascular responses to altered pressure, exercise, and hypoxia Further reading 2 - Central autonomic control Central autonomic control: overview Lower brainstem and autonomic reflexes Upper brainstem and integration of autonomic with arousal and stress responses Hypothalamus: central pattern generator for homeostasis and adaptation Amygdala: tagging of stimulus valence and innate survival responses Insular cortex: interoception, bodily awareness, and autonomic control Anterior cingulate cortex, predictive motor commands to autonomic nuclei Further reading 3 - Peripheral autonomic nervous system Introduction Sympathetic nervous system (SNS) Origin Outflow Neurotransmitters Central autonomic network Organization of SNS Sympathoadrenal axis and the adrenal gland Parasympathetic nervous system (PNS) Origin and outflow Neurotransmitters The concept of plurichemical transmission and chemical coding Visceral afferent neurons and autonomic nervous system Functional neuroanatomy and biochemical pharmacology Psychosocial stress and autonomic dysfunction Synucleinopathies and autonomic dysfunction Acknowledgments Further reading II - Biochemical and pharmacological mechanisms 4 - Noradrenergic neurotransmission Norepinephrine synthesis Norepinephrine storage Norepinephrine release Norepinephrine disposition and metabolism Noradrenergic innervation of the cardiovascular system Acknowledgment Further reading 5 - Antidepressant-sensitive norepinephrine transporters: structure and regulation NET structure, localization, and function Regulation of NET NET genetic variation and clinical implications Further reading 6 - α1-Adrenergic receptors α1-Adrenergic receptor (α1-AR) subtypes Structure of α1-adrenergic receptors Ligand binding and activation of α1-adrenergic receptors Signaling of α1-adrenergic receptors Regulation of α1-adrenergic receptors Function of α1-adrenergic receptors Acknowledgments Further reading 7 - Alpha2-adrenergic receptors Further reading 8 - β-Adrenergic receptors β-Adrenoreceptor subtypes Ligand binding and activation β-Adrenoreceptor desensitization Biological functions of β-adrenoreceptors Further reading 9 - Dopaminergic neurotransmission Introduction Central dopamine systems Disorders of central dopamine systems Peripheral dopamine systems Further reading 10 - Dopamine receptors Introduction Distribution and expression of dopamine receptors Central nervous system Autonomic nervous system Dopamine receptor structure Gene structure Receptor structure Dopamine receptor function: signal transduction pathways G protein dependent signaling Signal regulation β-Arrestin-dependent signaling Oligomerization Dopamine receptor pharmacology Ligand specificity Functional selectivity Further reading 11 - Cholinergic neurotransmission Acetylcholine biosynthesis and metabolism Acetylcholine receptors Cholinergic pharmacologic agents Further reading 12 - Acetylcholine and muscarinic receptors Cholinergic neurotransmission: sites and receptors Muscarinic agonists Muscarinic antagonists Further reading 13 - Nicotinic acetylcholine receptors in the autonomic nervous system Subtype diversity and distribution of nicotinic receptors Physiologic events associated with receptor activation Pharmacology of ganglion–type nicotinic receptors Further reading 14 - Neuropeptide Y and the autonomic nervous system Introduction NPY structure and receptors NPY functions Feedback in the autonomic nervous system Vasoconstriction Angiogenesis Myocardial contractility Cardiac remodeling NPY in the gastrointestinal tract Neuropeptide Y and cardiovascular disease Hypertension Atherosclerosis and plaque vulnerability Post myocardial infarction Arrhythmia Heart failure Conclusion Further reading 15 - Serotonin receptors Serotonin Synthesis and metabolism Neurotransmission Receptors Pharmacology and role in disease Role in autonomic processes Further reading 16 - Purinergic neurotransmission and nucleotide receptors Purinergic neurotransmission Receptors for purines and pyrimidines Conclusions Further reading 17 - Nitric oxide and the autonomic nervous system NO synthesis and actions Central NO–autonomic nervous system interactions NO–autonomic nervous system interactions in the periphery NO–autonomic nervous system interactions in heart rate control Conclusions Further reading 18 - Glutamatergic neurotransmission Synthesis and vesicular release Receptors Clearance of glutamate Glutamate metabolism Glutamate in the autonomic nervous system Glutamatergic drugs and the autonomic nervous system Summary Further reading 19 - Pharmacology: GABAergic neurotransmission Overview of GABA mediated signaling GABA responses are mediated by both ionotropic and metabotropic receptors GABAA receptors mediate multiple modes of neuronal signaling Neurotransmission is mediated by a diverse set of GABAA receptor subtypes Subtype-preferring drugs allow for selective components of GABA signaling Further reading 20 - Renin-angiotensin Introduction Components and features of the RAS Angiotensin II pathways Angiotensin-(1-7) pathways Emerging RAS pathways RAS: autonomic interactions for cardiovascular control RAS in clinical populations RAS therapies RAS in fetal programming of cardiovascular autonomic impairments RAS in cardiovascular autonomic disorders Adolescent orthostatic intolerance (OI) Postural orthostatic tachycardia syndrome (POTS) Primary autonomic failure Summary and gaps in knowledge Further reading 21 - Aldosterone, the mineralocorticoid receptor, and sympathetic nervous system The sympathetic nervous system and RAAS interact to maintain hemodynamic homeostasis Further reading Z2 - Vasopressin in central autonomic regulation VP structure, brain synthesis and release Modes of VP neurotransmission Vasopressin receptors in the brain—structure, distribution, and function VP in central autonomic regulation of circulation Hyperadrenergic conditions and central VP Central VP in regulation of respiration Central VP in regulation of body temperature Central VP in regulation of gastrointestinal tract, nausea, and vomiting Central VP in pain modulation Perspectives Further reading 23 - Calcitonin gene-related peptide and adrenomedullin Introduction α-CGRP peptide structure CGRP synthesis, localization, and release CGRP receptor CGRP-mediated cell signaling CGRP and CGRP agonists in the treatment of cardiovascular disease CGRP-antagonists for treatment of migraine Adrenomedullin and its role in the cardiovascular system Conclusion Acknowledgment Further reading 24 - Leptin signaling and energy homeostasis Introduction Leptin: from discovery to utility in understanding energy balance dysfunction Leptin receptor activation drives a variety of second messenger responses in the central nervous system Neuropeptide Y (NPY)/agouti-related peptide and anorexic pro-opiomelancortin cells are important mediators of leptin action ... Hypothalamic leptin and the regulation of metabolic homeostasis through actions at AGRP and POMC neurons Leptin acts as an important regulator of metabolism during fasting conditions Leptin influences autonomic outflow via POMC and NPY/AgRP neurons Leptin action outside of NPY/AgRP and POMC neurons also contributes to metabolic homeostasis Leptin regulation outside of NPY/AgRP and POMC action on autonomic sensory neuron activity in the periphery Questions for future study Further reading 25 - The endothelin system Introduction: endothelin system components Effects of preproET-1 or ET receptor gene deletion Mechanism of action of ET Pathophysiology of the endothelin system in experimental models Renal effects of ET-1 Cardiac effects of ET-1 ET-1 in essential hypertension Molecular genetics of the endothelin system Endothelins and the nervous system Role of endothelins (ETs) in the brain and sympathetic nervous system Conclusion Acknowledgments Further reading 26 - Pharmacology of the neurotransmission of the baro- and chemoreflex in the Nucleus Tractus Solitarius Introduction A logical analogy for a better view of NTS function Anatomy and physiology of NTS Major neurotransmitters in the NTS Glutamate and its receptors Postsynaptic glutamate receptors Presynaptic glutamate receptors Extrasynaptic glutamate receptors Astrocytes, glutamate receptors, and synaptic modulation Glutamate receptors and activation of GABA neurons Glutamate receptors and autonomic and respiratory function GABA and its receptors in the NTS GABAA receptors GABAC receptors GABAB receptors Astrocytes, GABA, and synaptic modulation GABA receptors and the autonomic and respiratory functions Other neurotransmitters and modulators in the NTS Further reading III Autonomic physiology 27 - Rhythms in sympathetic nerve activity Ubiquitous nature of biological rhythms The diversity of rhythms in SNA Functions of rhythms in SNA Using the rhythms in SNA to identify central sympathetic neurons Further reading 28 - Circadian rhythms and autonomic function The master clock SCN output and autonomic control Circadian and sleep control of the autonomic nervous system Circadian autonomic regulation: cardiovascular variables and metabolic control Conclusion Further reading 29 - Cardiorespiratory interactions in health and disease Introduction Cardiorespiratory interactions under resting conditions and physiological challenges The origin of cardiorespiratory coupling: the duet between the autonomic nervous system and respiratory central pattern gen ... Do changes in the respiratory-autonomic interactions play a role in cardiorespiratory diseases? Further reading 30 - Baroreceptor reflexes Neural pathways and effector mechanisms Arterial baroreflex Cardiopulmonary baroreflex Determinants of afferent baroreceptor activity Rate sensitivity of baroreceptors Large artery compliance Mechanoelectrical transduction and action potential discharge Baroreflex resetting and sensitivity in hypertension and other diseases Baroreflex adaptation and resetting in acute hypertension Baroreflex dysfunction in chronic hypertension, heart failure, and other diseases BRS: a determinant of cardiovascular risk and therapeutic target Further reading 31 - Cardiac and other visceral afferents Introduction Reflex control of the cardiovascular and viscera Structural and functional organization of visceral afferent signaling Afferents as central drivers of adverse remodeling of ANS in cardiovascular diseases Summary and conclusions Acknowledgments Further reading 32 - Sympathetic control of the heart Introduction A brief history Anatomy and physiology How cardiac myocytes receive and respond to sympathetic stimulation Pathophysiology Sympathetic-induced arrhythmic triggers Myocardial infarction Heart failure Inherited syndromes Future perspectives and therapeutic opportunities Further reading 33 - Cardiac vagal ganglia Extrinsic and intrinsic cardiac innervation Physiology of intracardiac neurons Anatomy and heterogeneity of intrinsic cardiac ganglia Pathophysiology in the intracardiac ganglia and therapeutic strategies Further reading 34 - Physiology of the upright posture Introduction Regulatory mechanisms involved in the adjustments of the human body to orthostatic stress Arterial baroreceptors Local vasoconstrictor mechanisms Role of capacitance vessels in orthostatic reflex adjustments Role of skeletal muscle pump Humoral mechanisms Further reading 35 - Cerebral circulation Basic considerations Neurovascular coupling Regulation of cerebral circulation Cerebral autoregulation Clinical considerations Role of autonomic innervation Cerebrovascular reactivity (CVR) Conclusion Further reading 36 - Autonomic control of the pupil Parasympatholytic (anticholinergic) drugs Parasympathomimetic (cholinergic) drugs Sympathomimetic (adrenergic) drugs Sympatholytic drugs (adrenergic blockers) Other agents Iris pigment and pupillary response to drugs Pupil sympathetic defects Pupil parasympathetic defects Pupil combined sympathetic and parasympathetic defects Acknowledgments Further reading 37 - Gastrointestinal function Introduction Gastrointestinal secretory functions Salivary secretion Gastric secretion Pancreaticobiliary secretion Bile Intestinal secretion and absorption Components controlling gastrointestinal motor functions Gastrointestinal muscle The enteric nervous system Extrinsic neural (autonomic nervous system) control The vagus nerve Normal gastrointestinal motor function Derangement of autonomic nervous system in disease states Further reading 38 - Extrinsic control of gastrointestinal function Parasympathetic control of the gastrointestinal tract Sympathetic control of the gastrointestinal tract Further reading 39 - The splanchnic circulation Overview Anatomy of the splanchnic circulation Local regulation of blood flow through the splanchnic organs Local regulation of blood storage in the splanchnic circulation Effects of the splanchnic circulation on overall circulatory function Sympathetic control of the splanchnic circulation—general features Sympathetic control of the splanchnic circulation in special circumstances Sympathetic control of the splanchnic circulation in disease Impaired splanchnic sympathetic drive Increased splanchnic sympathetic drive Neuromodulation therapy targeting the splanchnic sympathetic nerves Further reading 40 - Autonomic control of the kidney Introduction Innervation of the kidney Autonomic receptors in the kidney Reflex regulation of blood volume The inhibitory reno-renal reflex Autonomic control of the kidney in pathophysiological states Further reading 41 - Autonomic control of the lower urinary tract Introduction Neural circuits involved in reflex micturition control Peripheral nervous system Parasympathetic pathways Sympathetic pathways Somatic pathways Central neural control Organization of storage reflexes Spinal reflex pathways Supraspinal pathways Organization of voiding reflexes Spino-bulbo-spinal reflex pathways Neural circuits involved in voluntary micturition control Further reading 42 - Bladder function in health and disease Structure of the lower urinary tract Properties of the healthy lower urinary tract Clinical evaluation Clinical conditions Incontinence Bladder outlet obstruction Neurourology Painful bladder syndrome Conclusions Further reading 43 - Physiology and pathophysiology of female sexual function Physiology of the female sexual response cycle Sexual arousal Afferent and central pathways Neurotransmitters Innervation of female sexual function Hormones influencing female sexual function Common etiologies of female sexual dysfunction Neurogenic etiologies Assessment of female sexual dysfunction Laboratory investigation Common therapeutic approaches in female sexual dysfunction Further reading 44 - Regulation of sweating Anatomy and function of the sweat gland Type Density and distribution Physiology of sweat glands Function Innervation of sweat gland Denervation Further reading 45 - Autonomic innervation of the skeleton Bone sympathetic innervation: anatomy and ontogeny Sympathetic nerves and bone remodeling Sympathetic nerves, hematopoietic and cancer cell trafficking in the skeleton Sympathetic nerves and the endocrine function of the skeleton Conclusion Further reading 46 - Regulation of metabolism by the autonomic nervous system Basic considerations Contribution of the parasympathetic nervous system to satiety Contribution of the sympathoadrenal system to components of total daily energy expenditure Contribution of sympathetically stimulated organs/tissues to resting metabolic rate Mobilization/utilization of specific macronutrients: carbohydrate Mobilization/utilization of specific macronutrients: lipid Mobilization/utilization of specific macronutrients: protein Sympathetic regulation of Brown fat Role of the sympathoadrenal system in the dysregulation of metabolism Further reading 47 - Sex differences in autonomic function Introduction Physiological conditions Sympathetic activity Baroreflex function Neural-hemodynamic balance Pathophysiological conditions Obesity and related hypertension Hypertension and cardiovascular disease Conclusions Further reading 48 - Autonomic control during pregnancy Pregnancy activates the sympathetic nervous system Pregnancy impairs the baroreceptor reflex Mechanisms of pregnancy-induced baroreflex impairment Preeclampsia Summary and conclusions Further reading 49 - Aging and the autonomic nervous system Age-related changes in sympathetic activity Age-related changes in parasympathetic function Central autonomic pathways End-organ responsiveness Autonomic integration and baroreflex function Volume regulation Cerebral autoregulation Clinical consequences of age-related changes in autonomic function: hypertension and orthostatic hypotension Acknowledgments Further reading 50 - Autonomic function in sleep and sleep deprivation Stages of sleep Autonomic function during sleep NREM sleep REM sleep Autonomic responses to sleep deprivation Sleep deprivation Sleep restriction Insomnia Sleep apnea Conclusion Further reading 51 - Telemetric autonomic monitoring Introduction—why assess autonomic function using telemetry? Designing your experiment to maximize success and minimize stress Implantation for long-term nerve recordings Validating your nerve signal Quantifying your nerve signal Summary Further reading IV Autonomic response to environmental challenges 52 - Exercise Introduction Acute exercise Exercise training Exercise as a non-drug therapy Conclusion Further reading 53 - Psychological stress and the autonomic nervous system Introduction Psychological stress and autonomic activity Normal psychological stresses and autonomic activity Patterns of autonomic response to stress Heart rate variability and cardiac disease Gastrointestinal (GI) control Psychosomatic disorders and the autonomic nervous system Posttraumatic stress disorder, panic, and anxiety Acknowledgment Further reading 54 - Hypoglycemia Normal mechanisms of glucose regulation Impaired counterregulatory responses to hypoglycemia in diabetes (DM) Impaired counterregulatory responses to hypoglycemia in autonomic failure (AF) Hypoglycemia-associated autonomic failure (HAAF) Further reading 55 - Autonomic response to hypovolemic shock Introduction Mechanisms of autonomic compensation Other factors that influence compensatory responses to hypovolemia Conclusion Disclaimer Further reading 56 - Physiology of thermoregulation: central and peripheral mechanisms Introduction Peripheral (outside the brain) physiological mechanisms of thermoregulation Regulation of body temperature in thermoneutral environments Physiological responses to cold exposure Physiological responses to heat exposure Skin blood flow Sweating Assessment of integrative physiological thermoregulation in humans Central neural control of thermoregulation Central responses to thermal stimulation of the skin surface Integration of afferent and efferent neural signals in the POA Thermoregulatory effector drive from the dorsomedial hypothalamus Rostral raphe pallidus area contains premotor neurons for thermoregulatory effectors Spinal sympathetic mechanisms controlling thermal effectors Summary of central mechanisms Overall summary Disclaimer Further reading 57 - Effects of high altitude Introduction Hyperacute altitude exposure Acute altitude exposure Acute mountain sickness (AMS) and high altitude cerebral edema (HACE) High altitude pulmonary edema (HAPE) Chronic altitude exposure and chronic mountain sickness (CMS) Summary and key unanswered questions Further reading 58 - Space physiology Introduction Space motion sickness Orthostatic intolerance Clinical interactions Further reading 59 - Noise, air pollution, and the autonomic nervous system Background Health risks Epidemiological evidence suggesting autonomic involvement Animal studies Human investigations Underlying mechanisms Areas of uncertainty Further reading V Pathophysiological mechanisms 60 - The autonomic inflammatory reflex The autonomic inflammatory reflex What is an inflammatory reflex? Is there a role for the vagus nerve in the systemic inflammatory reflex? The splanchnic sympathetic nerve mediates an inflammatory reflex The efferent limb of the inflammatory reflex and its reach within abdominal organs The afferent limb of the inflammatory reflex: neural and/or humoral? What is the significance of the splanchnic inflammatory reflex? Concluding comments Acknowledgments Further reading 61 - Reactive oxygen species and oxidative stress Introduction Biochemistry of reactive oxygen species Production of reactive oxygen species in the ANS Xanthine oxidase Uncoupled nitric oxide synthase Mitochondrial respiratory enzymes Endoplasmic reticulum and reactive oxygen species generation ROS-generating NADPH oxidases NADPH oxidases Regulation of noxs Protecting against oxidative stress—antioxidant defenses Molecular and cellular effects of oxidative stress Redox signaling Oxidative posttranslational modifications ROS and the autonomic nervous system Physiology of ROS in the ANS Oxidative stress and pathological processes in the ANS Conclusions Acknowledgment Further reading 62 - Insulin resistance and the autonomic nervous system Introduction Obesity and insulin resistance Obesity and sympathetic activity Contribution of sympathetic activity to insulin resistance in obesity Contribution of sympathetic activity to insulin resistance in PCOS Conclusions Further reading 63 - Salt sensitivity of blood pressure Prognosis of SSBP Mechanisms of SSBP Interstitial Na+ and SSBP Immunity and SSBP Genetics of SSBP Environmental factors Diagnosis of SSBP Treatment of SSBP Further reading 64 - Airway afferent nerves Introduction Extrinsic innervation of airway afferents Characterization of airway afferent subtypes C-fibers A-fibers Mechanisms of activation C-fiber activation Transient receptor potential (TRP) channels A-fiber activation Voltage-gated sodium channels (NaV) Physiological consequence of airway afferent activation Consequences of airway C-fiber activation Consequences of A-fiber activation Role of airway afferent nerves in respiratory diseases Summary Suggestions for further reading VI Evaluation of autonomic function 65 - Clinical evaluation of autonomic disorders Approach in history taking Assessment: bedside and laboratory testing Final thoughts Further reading 66 - Autonomic function testing Introduction Aims of and clinical indications for autonomic testing The autonomic reflex screen Evaluation of cardiovagal function Heart rate response to deep breathing Valsalva ratio Tests of cardiovascular adrenergic function Blood pressure responses to the Valsalva maneuver Blood pressure response to head-up tilt Further reading 67 - Tilt table testing Head-up tilt table (HUTT) test: background What is HUTT? Physiology of the HUTT Are there different types of HUTT testing protocols? What kind of monitoring is involved during HUTT testing? Indications for HUTT testing Utility and clinical applications of HUTT testing “Sweet-Spot” for HUTT HUTT in postural tachycardia syndrome (POTS) HUTT in orthostatic hypotension (OH) Conclusions Further reading 68 - Patient symptom and rating scales: OHQ, COMPASS, UMSARS Introduction The orthostatic hypotension questionnaire (OHQ) The composite autonomic symptom score (COMPASS) The unified multiple system atrophy rating scale (UMSARS) Further reading 69 - Sympathetic microneurography and clinical applications Microelectrode recordings of sympathetic nerve activity in humans Analysis of multiunit sympathetic nerve activity Muscle sympathetic nerve activity in health and disease Orthostatic hypotension and syncope Cardiovascular, respiratory, and renal disease Neurological and psychiatric disorders Skin sympathetic nerve activity in health and disease Disorders of thermoregulation Conclusions Further reading 70 - Assessment of the autonomic control of the cardiovascular system by a frequency domain approach Introduction The frequency domain approach for exploring cardiovascular and sympathetic discharge variability and their relationship wit ... The frequency domain approach for exploring baroreceptor function during carotid baroreceptor rhythmic stimulation The frequency domain approach for exploring autonomic and baroreceptor abnormalities during orthostatic presyncope Conclusions Further reading 71 - Evaluation of sudomotor function Introduction Quantitative sudomotor axon reflex test Neurophysiology Technique Clinical implications Quantitative direct and indirect test of sudomotor function Silicone imprint Neuropad Sympathetic skin response Electrochemical skin conductance Thermoregulatory sweat test Summary Further reading 72 - Plasma catechols Primer on the autonomic nervous system Sources and meanings of plasma levels of catechols DHPG DA DOPAC EPI DOPA Cys-DOPA Cys-DA Diagnostic abnormal patterns of plasma catechols DBH deficiency LAAAD deficiency Menkes disease Supportive abnormal patterns of plasma catechols Evoked changes in plasma catechol levels Orthostatic NE responses to identify neurogenic orthostatic hypotension (nOH) Orthostatic catecholamines in chronic orthostatic intolerance syndromes Conclusions Acknowledgment Further reading 73 - Imaging cortical and subcortical sites involved in cardiovascular control Functional identification of the medullary circuitry subserving the arterial baroreflex in humans Functional identification of areas above the brainstem involved in blood pressure control Functional significance of the sympathetic connectome Conclusions Acknowledgments Further reading 74 - Clinical sympathetic neuroimaging Sympathetic imaging and methods Sympathetic neuroimaging in clinical autonomic disorders Sympathetic neuroimaging in the diagnosis of LBDs Sympathetic neuroimaging as a biomarker of catecholaminergic dysfunction in LBDs Further reading 75 - Cutaneous autonomic innervation: assessment by skin biopsy Introduction Cutaneous neuroanatomy Sweat glands Hair follicles Arrector pilorum muscles Blood vessels Skin biopsies to evaluate specific autonomic disorders Recent advances in skin biopsies Summary Further reading 76 - Sympatho-effector transduction Sympatho-effector transduction Assessment of sympatho-effector transduction Sympatho-effector transduction in health and disease Conclusions Further reading VII - Cardiovascular disorders 77 - Neurally mediated syncope (Autonomically mediated syncope) Background Pathophysiology of vasovagal syncope Natural history of VVS Diagnosis of VVS Role of head-up tilt table testing Management strategies Other specific NMS/AMS entities Hypersensitive carotid sinus syndrome (HSCSS) Situational syncope Conclusions Further reading 78 - Orthostatic hypotension Autonomic mechanisms that maintain upright blood pressure Definition, epidemiology, and clinical relevance Etiology Evaluation of the patient with orthostatic hypotension Conclusions Further reading 79 - Spectrum of orthostatic hypotension Introduction Initial OH Delayed OH Hyperadrenergic OH Management of orthostatic hypotension Conclusions Further reading 80 - Baroreflex failure Introduction Causes of baroreflex failure Clinical presentation Diagnosing baroreflex failure Treatment Further reading 81 - Essential hypertension Guidelines' recommendation Consequences of differences between recommendations Sympathetic overdrive Hypertension-related target organ damage Therapeutic implications Further reading 82 - Obesity-associated hypertension Epidemiology and significance Increased sympathetic activity in obesity—association studies Not all obesity is associated with sympathetic activation Mechanisms explaining sympathetic activation in obesity Does sympathetic activation provide any beneficial effect in obesity? Potential deleterious effects of sympathetic activation in obesity Implications Further reading 83 - Pheochromocytoma and paraganglioma Introduction Clinical presentation Genetics Biochemical diagnosis Tumor localization Pre to postoperative patient management Pathology and metastatic disease Further reading 84 - Autonomic dysfunction in heart failure Heart failure Autonomic disturbances in heart failure with reduced ejection fraction Autonomic disturbances in heart failure with preserved ejection fraction Clinical considerations and future directions Further reading 85 - Myocardial stunning and takotsubo cardiomyopathy Introduction Pathophysiology Triggers Cardiology findings Autonomic studies in the acute phase Autonomic studies after recovery Predisposition and susceptibility Further reading 86 - The autonomic nervous system and cardiac arrhythmias Introduction Anatomy of the cardiac autonomic nervous system Neural remodeling and autonomic dysregulation in arrhythmias Atrial fibrillation Ventricular arrhythmias Neuromodulatory interventions for arrhythmia management Atrial fibrillation Ventricular tachycardia Conclusion Further reading VIII Congenital autonomic disorders 87 - Deficiencies of tetrahydrobiopterin, tyrosine hydroxylase, and aromatic L-amino acid decarboxylase Biochemistry Presentation and neurological symptoms Diagnosis Tetrahydrobiopterin deficiencies Tyrosine hydroxylase deficiency Aromatic L-amino acid decarboxylase deficiency Treatment BH4 deficiencies TH deficiency AADC deficiency Further reading 88 - Congenital disorders of noradrenergic neurotransmission Familial autonomic ganglionopathy Dopamine-β-hydroxylase (DBH) deficiency Cyt "The Primer on the autonomic nervous system, fourth edition aims to provide an inclusive and accessible overview of autonomic neuroscience for students, scientists, and clinicians. Its 142 chapters draw on the expertise of more than 215 basic scientists and clinicians and discuss key information on how the autonomic nervous system controls the body in response to stress and disease. Each concise chapter provides the basic knowledge of a given topic and guides the reader to key references for more in-depth information. This edition builds upon the principles of the prior éditions, while focusing on the translational crossover between basic and clinical research. In addition to comprehensively covering all aspects of autonomic physiology and pathology, the new edition features new developments in autonomic neuroscience including modulation of nerve function, optogenetics, gene therapy, novel imaging techniques and drug repurposing to treat autonomic disorders."