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1.
Revista Digital de Postgrado ; 9(2): 207, ago. 2020. graf
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1102940

RESUMO

La pancreatitis es una de las consecuencias principales del envenenamiento escorpiónico producido por el género Tityus. El manejo farmacológico mediante el uso de agonistas y antagonistas α adrenérgicos en modelos experimentales in vivo e in vitro, permiten establecer una aproximación del papel del Sistema Nervioso Simpático (SNS) en el desarrollo de la pancreatitis. Objetivo: determinar el papel del SNS en el desarrollo de la pancreatitis aguda inducida por el veneno de escorpión Tityus zulianus (TzV), por medio del uso de simpaticolíticos como la clonidina y el prazosin. Métodos: La Extravasación de Proteínas Plasmáticas (EPP) en el páncreas se evaluó mediante el método de Azul de Evans (AE), modificado de Saria y Lundberg (1983) a 620 nm; n=3 ratones NIH en cada grupo experimental. Las comparaciones se hicieron por ANOVA de una vía y las pruebas post HOC por Tukey-Kramer. Resultados: Ambos fármacos (1mg/Kg), disminuyeron significativamente p< 0,01 (**) la EPP en el páncreas inducida por el TzV, en comparación con los animales inoculados solo con TzV. No hubo diferencias significativas entre los animales del grupo control y los grupos tratados con los fármacos más el TzV. Conclusiones: El efecto pancreatotóxico del TzV en ratones podría tener un componente autonómico dado que drogas simpaticolíticas al disminuir la actividad noradrenérgica reducen la magnitud del edema. Esto sugiere que ambos fármacos pueden usarse como estrategia terapéutica en estos casos(AU)


Pancreatitis is one of the main consequences of scorpionic poisoning produced by the genus Tityus. The pharmacological management through the use of agonists and α adrenergic antagonists in experimental models in vivo and in vitro, allow us to establish an approximation of the role of the Sympathetic Nervous System (SNS) in the development of pancreatitis. Objective: to determine the role of SNS in the development of acute pancreatitis induced by the scorpion venom Tityus zulianus (TzV), through the use of sympatholytics such as clonidine and prazosin. Methods: Plasma Protein Extravasation (PPE) in the pancreas was evaluated by the method of Evans Blue (EA), modified by Saria and Lundberg (1983) at 620 nm; n = 3 NIH mice in each experimental group. Comparisons were made by one-way ANOVA and post-HOC tests by Tukey-Kramer. Results: Both drugs (1mg / Kg) significantly decreased p <0.01 (**) the EPP in the pancreas induced by TzV, compared to animals inoculated only with TzV. There were no significant differences between the animals in the control group and the groups treated with drugs plus TzV. Conclusions: The pancreatotoxic effect of TzV in mice could have an autonomic component since sympatholytic drugs by decreasing noradrenergic activity reduce the magnitude of edema. This suggests that both drugs can be used as a therapeutic strategy in these cases(AU)


Assuntos
Animais , Camundongos , Pancreatite/etiologia , Venenos de Escorpião , Sistema Nervoso Simpático/efeitos dos fármacos , Farmacologia Clínica , Prazosina/uso terapêutico , Clonidina/uso terapêutico
2.
Cardiovasc Ther ; 2020: 1321782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695226

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.


Assuntos
Doenças Cardiovasculares/etiologia , Frequência Cardíaca , Coração/inervação , Hidradenite Supurativa/complicações , Sistema Nervoso Parassimpático/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adolescente , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Feminino , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Adulto Jovem
3.
Orv Hetil ; 161(29): 1190-1199, 2020 07.
Artigo em Húngaro | MEDLINE | ID: mdl-32628618

RESUMO

Heart failure is a rapidly growing epidemic in developed countries. It has been well documented that heart failure is associated with abnormal neurohumoral activation. The autonomic regulation is characterized by decreased parasympathetic and elevated sympathetic activity. While the cardiovagal activity could be easily assessed by various heart rate variability parameters, markers of the sympathetic activity are not readily available. Percutaneous insertion of microelectrodes in a peripheral nerve allows recording of the muscle sympathetic vasomotor nerve activity (MSNA). MSNA shows good correlation with the cardiac sympathetic activity, and also with the levels of circulating catecholamines. Besides determination of the baseline sympathetic activity, rapid sympathetic responses to various stimuli can be also described by changes of MSNA. Elevated MSNA has been documented in several diseases, including hypertension, obesity, myocardial ischemia and renal failure. In heart failure, the elevated MSNA is well correlated to the clinical severity of the patient's conditions, and serves as a prognostic marker of mortality. In our paper, we give a short account of the history of MSNA studies, describe its physiological background and clinical relevance with special regard to heart failure. Orv Hetil. 2020; 161(29): 1190-1199.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Músculos/inervação , Frequência Cardíaca/fisiologia , Humanos , Hipertensão , Sistema Nervoso Simpático/fisiopatologia
4.
Ther Adv Cardiovasc Dis ; 14: 1753944720939383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32715944

RESUMO

This review focuses on the pathogenic role of sodium glucose cotransporter (SGLT)-2 in the development of renal dysfunction and heart failure in patients with diabetes, by emphasizing the concept of reno-cardiac syndrome (kidney injury worsens cardiac condition) and by substantiating the deleterious effect of sympathetic overdrive in this context. Furthermore, the review proposes a mechanistic hypothesis to explain the benefits of SGLT2 inhibitors, specifically that SGLT-2 inhibitors reduce sympathetic activation at the renal level. To illustrate this point, several examples from both animal experiments and clinical observations are introduced. The bidirectional interaction of the heart and kidney were deeply implicated as an exacerbator of heart failure and renal failure without diabetes. Renal cortical ischemia and abnormal glucose metabolism of tubular epithelial cells are likely to exist as common pathologies in nondiabetic heart failure patients. It is no wonder why SGLT-2 inhibitors are specifically being studied even in the absence of diabetes, both for heart failure and also for renal failure.


Assuntos
Síndrome Cardiorrenal/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Coração/inervação , Rim/inervação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Síndrome Cardiorrenal/mortalidade , Síndrome Cardiorrenal/fisiopatologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Sistema Nervoso Simpático/fisiopatologia , Resultado do Tratamento
5.
Nature ; 583(7816): 441-446, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641826

RESUMO

Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content1, regulating both physiological intestinal functions such as nutrient absorption and motility2,3, and brain-wired feeding behaviour2. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology4. Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations. We find that the gut microbiome modulates gut-extrinsic sympathetic neurons: microbiota depletion leads to increased expression of the neuronal transcription factor cFos, and colonization of germ-free mice with bacteria that produce short-chain fatty acids suppresses cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling and anterograde tracing identify a subset of distal intestine-projecting vagal neurons that are positioned to have an afferent role in microbiota-mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identifies brainstem sensory nuclei that are activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota-dependent control of gut-extrinsic sympathetic activation through a gut-brain circuit.


Assuntos
Microbioma Gastrointestinal/fisiologia , Intestinos/inervação , Neurônios/fisiologia , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/fisiologia , Animais , Disbiose/fisiopatologia , Feminino , Gânglios Simpáticos/citologia , Gânglios Simpáticos/fisiologia , Motilidade Gastrointestinal , Vida Livre de Germes , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Vias Neurais/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transcriptoma
6.
Exp Psychol ; 67(2): 77-87, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32729404

RESUMO

The intriguing interplay between acute stress physiology and cognitive processes has long been noted. However, while stress-induced release of glucocorticoids has repeatedly been shown to impact brain mechanisms underlying cognition and memory, less experimental research addressed the effects of stress-induced central sympathetic nervous system (SNS) activation on cognitive performance. Moreover, despite the long-standing notion that the way performance is modulated by arousal may crucially depend on task complexity, mechanistic research demonstrating a direct, causal influence of altered SNS activity is scarce. Twelve healthy men participated in a placebo-controlled, pharmacologic dose-response study involving three within-subject assessments (1-week intervals). Subjective and objective indices of SNS activity as well as reaction time (RT) in three different tasks varying in cognitive demand (simple RT, choice RT, and verbal RT in complex mental arithmetic) were assessed during modulation of central SNS tone by intravenous infusions of dexmedetomidine (alpha2-agonist), yohimbine (alpha2-antagonist), and placebo. Cognitive performance was negatively affected by alpha2-agonism in all task conditions. By contrast, administration of yohimbine improved simple RT, while diminishing complex RT, supporting the assumption of a nonlinear way of action depending on task characteristics. Our results highlight the consequences of central (noradrenergic) SNS activation for cognitive-motor performance in RT tasks of varying complexity.


Assuntos
Cognição/fisiologia , Desempenho Psicomotor/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
7.
Nat Commun ; 11(1): 2847, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504036

RESUMO

The browning of white adipose tissue (WAT) has got much attention for its potential beneficial effects on metabolic disorders, however, the nutritional factors and neuronal signals involved remain largely unknown. We sought to investigate whether WAT browning is stimulated by leucine deprivation, and whether the amino acid sensor, general control non-derepressible 2 (GCN2), in amygdalar protein kinase C-δ (PKC-δ) neurons contributes to this regulation. Our results show that leucine deficiency can induce WAT browning, which is unlikely to be caused by food intake, but is largely blocked by PKC-δ neuronal inhibition and amygdalar GCN2 deletion. Furthermore, GCN2 knockdown in amygdalar PKC-δ neurons blocks WAT browning, which is reversed by over-expression of amino acid responsive gene activating transcription factor 4 (ATF4), and is mediated by the activities of amygdalar PKC-δ neurons and the sympathetic nervous system. Our data demonstrate that GCN2/ATF4 can regulate WAT browning in amygdalar PKC-δ neurons under leucine deprivation.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Tecido Adiposo Branco/fisiologia , Tonsila do Cerebelo/fisiologia , Leucina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/inervação , Tonsila do Cerebelo/citologia , Animais , Técnicas de Silenciamento de Genes , Lipólise/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Proteína Quinase C-delta/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/fisiologia , Técnicas Estereotáxicas , Sistema Nervoso Simpático/fisiologia , Termogênese/fisiologia
8.
Ideggyogy Sz ; 73(05-06): 185-188, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32579308

RESUMO

Background and purpose: After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose - The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Methods: Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. Results: A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Conclusion: Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Síndrome do Túnel Carpal/cirurgia , Resposta Galvânica da Pele/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Nervo Mediano , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Complicações Pós-Operatórias , Resultado do Tratamento , Nervo Ulnar/fisiologia , Nervo Ulnar/fisiopatologia
9.
Curr Opin Cardiol ; 35(4): 389-396, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398606

RESUMO

PURPOSE OF REVIEW: The obesity epidemic is progressively affecting majority of individuals worldwide leading to many adverse metabolic and cardiovascular outcomes. Increasingly concerning among them is obesity hypertension (HTN). In this review, we delve into the physiology and therapeutic options in obesity HTN as we discuss the implications of obesity HTN on society. RECENT FINDINGS: Obesity is the most common cause of primary HTN and is directly proportional to increases BMI. The significance of adiposity in obesity HTN centers on humoral mechanisms via stimulation of the renal-angiotensin system, leptin activity, sympathetic overdrive, and proinflammatory processes that potentiate vascular remodeling, which results in a higher incidence of the progression of many known serious cardiovascular diseases. Although lifestyle and medical therapies have been recommended for obesity and its sequelae, continued global progression of this disease has driven the development of newer therapies such as carotid baroreflex activation therapy, renal denervation, and selective leptin receptor antagonism. SUMMARY: The pathophysiology of obesity HTN has not yet been fully elucidated despite it being one of the oldest known diseases to mankind. Major efforts to understand obesity HTN endures, paving opportunities for newer and possibly superior therapeutic options.


Assuntos
Hipertensão/terapia , Sistema Nervoso Simpático , Barorreflexo , Humanos , Rim , Obesidade/terapia
10.
Proc Natl Acad Sci U S A ; 117(23): 13078-13083, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32434910

RESUMO

The central nervous system both influences and is influenced by the gastrointestinal system. Most research on this gut-brain connection has focused on how ascending signals from the gut and its microbiome alter brain function. Less attention has focused on how descending signals from the central nervous system alter gut function. Here, we used retrograde transneuronal transport of rabies virus to identify the cortical areas that most directly influence parasympathetic and sympathetic control of the rat stomach. Cortical neurons that influence parasympathetic output to the stomach originated from the rostral insula and portions of medial prefrontal cortex, regions that are associated with interoception and emotional control. In contrast, cortical neurons that influence sympathetic output to the stomach originated overwhelmingly from the primary motor cortex, primary somatosensory cortex, and secondary motor cortex, regions that are linked to skeletomotor control and action. Clearly, the two limbs of autonomic control over the stomach are influenced by distinct cortical networks.


Assuntos
Córtex Cerebral/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Estômago/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Mapeamento Encefálico , Masculino , Vias Neurais/fisiologia , Ratos , Estômago/inervação
11.
J Vasc Res ; 57(3): 152-163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248195

RESUMO

Palmitoylethanolamide is an endogenous lipid that exerts complex vascular effects, enhances the effects of endocannabinoids and induces a direct hypotension, but the mechanisms involved have been poorly explored. Hence, this study investigated in Wistar pithed rats the role of CB1, CB2, TRPV1 and GPR55 receptors in the inhibition by palmitoylethanolamide of the vasopressor responses produced by sympathetic stimulation or exogenous noradrenaline. Frequency- and dose-dependent vasopressor responses were analysed before and during intravenous (i.v.) continuous infusions of palmitoylethanolamide in animals receiving i.v. bolus of the antagonists NIDA41020 (CB1), AM630 (CB2), capsazepine (TRPV1), and/or cannabidiol (GPR55). Palmitoyletha-nolamide (0.1-3.1 µg/kg/min) dose-dependently inhibited the sympathetically induced and noradrenaline-induced vasopressor responses. Both inhibitions were: (i) partially blocked by 100 µg/kg NIDA41020, 100 µg/kg capsazepine, or 31 µg/kg cannabidiol; (ii) unaffected by 310 µg/kg AM630; and (iii) abolished by the combination NIDA41020 + capsazepine + cannabidiol (100, 100, and 31 µg/kg, respectively). The resting blood pressure was decreased by palmitoylethanolamide (effect prevented by NIDA41020, capsazepine or cannabidiol, but not by AM630). These results suggest that: (i) palmitoylethanolamide inhibits the vasopressor responses to sympathetic stimulation and exogenous noradrenaline and that it induces hypotension; and (ii) all these effects are mediated by prejunctional and vascular CB1, TRPV1 and probably GPR55, but not by CB2, receptors.


Assuntos
Artérias/efeitos dos fármacos , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Artérias/inervação , Artérias/metabolismo , Estado de Descerebração , Estimulação Elétrica , Masculino , Norepinefrina/farmacologia , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Receptores de Canabinoides/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Sistema Nervoso Simpático/fisiologia , Simpatomiméticos/farmacologia , Canais de Cátion TRPV/metabolismo
12.
Nat Commun ; 11(1): 1517, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251290

RESUMO

Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fígado Gorduroso/patologia , Resistência à Insulina , Neurônios/metabolismo , Obesidade/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Tecido Adiposo Marrom/inervação , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Feminino , Técnicas de Introdução de Genes , Técnicas de Inativação de Genes , Humanos , Hipotálamo/patologia , Leptina/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Transgênicos , Obesidade/etiologia , Receptores para Leptina/metabolismo , Sistema Nervoso Simpático/fisiologia , Termogênese/fisiologia
13.
Nat Protoc ; 15(5): 1853-1877, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32313253

RESUMO

neuECG, the simultaneous noninvasive recording of ECG and skin sympathetic nerve activity (SKNA), directly records sympathetic nerve activity over a long period of time. It can be used to measure sympathetic tone in healthy subjects and in subjects with non-cardiovascular diseases. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the SKNA. neuECG is voltage calibrated and does not require invasive procedures to impale electrodes in nerves and thus has advantages over microneurography. Here, we present a protocol that takes <10 min to set up. The neuECG can be continuously recorded over a 24-h period or longer. We also describe methods to efficiently analyze neuECG from humans using commercially available hardware and software to facilitate adoption of this technology in clinical research.


Assuntos
Técnicas de Diagnóstico Neurológico , Eletrocardiografia , Sistema Nervoso Simpático , Voluntários Saudáveis , Humanos , Pele/inervação
14.
PLoS One ; 15(4): e0227721, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298298

RESUMO

Speech fluency can be impaired in stressful situations. In this study, it was investigated whether a verbal fluency task by itself, i.e. without the presence of any further stressors, induces responses of the hypothalamic-pituitary adrenal (HPA) axis and of the sympathetic nervous system (SNS). The sample consisted of n = 85 participants (68.2% female; 33.3 ± 15.2 years) who performed two consecutive verbal fluency tasks for two minutes each. The categories were either 'stress' or 'disease' and 'animals' or 'foods' which were presented in a randomized order. Three saliva samples were collected, prior to the task (t0), immediately after (t1), and ten minutes after it (t2). Salivary α-amylase and cortisol were assessed. Furthermore, blood pressure, heart rate, and ratings of actual stress perception, level of effort, and tiredness were measured. The verbal fluency task induced a HPA axis response with a maximum cortisol level at t2 which was independent of task performance. Furthermore, perceived stress and effort, as well as tiredness increased after the task. Moreover, tiredness immediately after the task was negatively correlated with task performance. No α-amylase, blood pressure, or heart rate, and therefore SNS, responses were found. Implications for the integrated specificity model are discussed. We conclude that a verbal fluency task acts like an acute stressor that induces a cortisol and a perceived stress response without the need for further (e.g., social-evaluative) stress components. Therefore, it is a less time-consuming alternative to other stress tasks that can be used in field studies with little effort.


Assuntos
Cognição/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Fala/fisiologia , Estresse Psicológico/metabolismo , Adolescente , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/química , alfa-Amilases Salivares/análise , alfa-Amilases Salivares/metabolismo , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Adulto Jovem
15.
Am J Physiol Heart Circ Physiol ; 318(5): H1198-H1207, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243771

RESUMO

Posttraumatic stress disorder (PTSD) is more prevalent in women and associated with greater risk of major forms of cardiovascular disease, but physiological mechanisms underlying this association remain unknown. We hypothesized that abnormal sympathetic responses to sympathoexcitatory stimuli might predispose PTSD patients to a greater risk of cardiovascular disease. We examined changes in integrated muscle sympathetic nerve activity (MSNA) burst and multiunit action potential (AP) recruitment patterns as well as hemodynamic responses during cold pressor test (CPT) in 14 women with PTSD and 14 healthy control subjects. Data were collected during 1-min baseline, 2-min CPT, and 3-min recovery. At baseline, blood pressure (BP) was not different between groups; however, heart rate and sympathetic neural activity were greater in women with PTSD [MSNA burst frequency (BF): 27 ± 13 vs. 18 ± 14 bursts/min (P = 0.04); AP frequency: 272 ± 152 vs. 174 ± 146 spikes/min (P = 0.03)]. In response to CPT, BP responses exhibited a significant group × time interaction (P = 0.01) highlighted by a significant diastolic BP main group effect (P = 0.048) despite the finding that increases in integrated MSNA burst responses were not different between groups (P > 0.05). However, compared with control subjects, AP firing frequency (group × time interaction P = 0.0001, group P = 0.02) and AP per burst (group × time interaction P = 0.03, group P = 0.03) were augmented in women with PTSD. Collectively, women with PTSD exhibited a greater pressor response and an exaggerated sympathetic neural recruitment pattern during sympathoexcitatory stimuli that may, in part, explain the propensity toward developing hypertension and cardiovascular disease later in life.NEW & NOTEWORTHY The novel findings of the present study are that women with posttraumatic stress disorder (PTSD) have an augmented pressor response to the sympathoexcitatory stimulus of a cold pressor test (CPT) compared with healthy control subjects. Although integrated muscle sympathetic nerve activity burst responses were not significantly different between groups, total sympathetic action potential discharge in response to the CPT was markedly elevated in women with PTSD exhibiting increased firing of low-threshold axons as well as the recruitment of latent subpopulations of larger-sized axons that are otherwise silent at baseline. Aberrant autonomic circulatory control in response to sympathoexcitatory stimulus may in part explain the propensity toward developing hypertension and cardiovascular disease in this population.


Assuntos
Pressão Sanguínea , Recrutamento Neurofisiológico , Reflexo , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Potenciais de Ação , Adulto , Temperatura Baixa , Feminino , Humanos , Pessoa de Meia-Idade
16.
PLoS One ; 15(4): e0231659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324756

RESUMO

Pathological fear and anxiety disorders can have debilitating impacts on individual patients and society. The neural circuitry underlying fear learning and extinction has been known to play a crucial role in the development and maintenance of anxiety disorders. Pavlovian conditioning, where a subject learns an association between a biologically-relevant stimulus and a neutral cue, has been instrumental in guiding the development of therapies for treating anxiety disorders. To date, a number of physiological signal responses such as skin conductance, heart rate, electroencephalography and cerebral blood flow have been analyzed in Pavlovian fear conditioning experiments. However, physiological markers are often examined separately to gain insight into the neural processes underlying fear acquisition. We propose a method to track a single brain-related sympathetic arousal state from physiological signal features during fear conditioning. We develop a state-space formulation that probabilistically relates features from skin conductance and heart rate to the unobserved sympathetic arousal state. We use an expectation-maximization framework for state estimation and model parameter recovery. State estimation is performed via Bayesian filtering. We evaluate our model on simulated and experimental data acquired in a trace fear conditioning experiment. Results on simulated data show the ability of our proposed method to estimate an unobserved arousal state and recover model parameters. Results on experimental data are consistent with skin conductance measurements and provide good fits to heartbeats modeled as a binary point process. The ability to track arousal from skin conductance and heart rate within a state-space model is an important precursor to the development of wearable monitors that could aid in patient care. Anxiety and trauma-related disorders are often accompanied by a heightened sympathetic tone and the methods described herein could find clinical applications in remote monitoring for therapeutic purposes.


Assuntos
Algoritmos , Nível de Alerta/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Resposta Galvânica da Pele/fisiologia , Frequência Cardíaca/fisiologia , Sistema Nervoso Simpático/fisiologia , Simulação por Computador , Feminino , Humanos , Masculino , Adulto Jovem
17.
Nutr Metab Cardiovasc Dis ; 30(6): 1023-1031, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32249140

RESUMO

BACKGROUND AND AIMS: Consumption of a high caloric diet induces autonomic imbalance, which can lead to cardiovascular disease. Impaired arterial baroreflex control is suggested to play an important role in cardiovascular autonomic imbalance, often seen in obesity. We previously demonstrated that cafeteria diets increase the sympathetic drive to white and brown adipose tissue. METHODS AND RESULTS: After feeding a cafeteria diet to rats for 26 days, we evaluated: (i)heart rate (HR) and arterial pressure (AP); (ii)baroreflex and chemoreflex function; and (iii) autonomic modulation of the heart and vessels, measured through pulse interval (PI) and systolic arterial pressure (SAP) variability analyses and following administration of autonomic blockers. The cafeteria diet increased body fat mass and serum insulin, leptin, triacylglycerol and cholesterol levels. Baseline HR (15%) was also increased, accompanied by increased power in the low frequency band (60%) and in the low frequency/high frequency ratio (104%) in the PI spectra. Nonlinear analysis revealed an increased occurrence of 0V (39%) and decreased occurrence of 2UV (18%) patterns. Following administration of autonomic blockers, we observed an increase in cardiac sympathetic tone (425%) in cafeteria diet-fed rats. The cafeteria diet had no effect on AP, SAP variability, baroreflex and chemoreflex control. CONCLUSION: Our findings suggest that consumption of a cafeteria diet increases sympathetic drive to the heart but not to the blood vessels, independent of impairment in baroreflex and chemoreflex functions. Other mechanisms may be involved in the increased cardiac sympathetic drive, and compensatory vascular mechanisms may prevent the development of hypertension in this model of obesity.


Assuntos
Barorreflexo , Células Quimiorreceptoras/metabolismo , Dieta , Ingestão de Energia , Coração/inervação , Obesidade/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Pressão Arterial , Modelos Animais de Doenças , Frequência Cardíaca , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Ratos Wistar , Fatores de Tempo
18.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R961-R971, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32267729

RESUMO

We examined the effect of acute intermittent hypoxia (IH) on sympathetic neural firing patterns and the role of the carotid chemoreceptors. We hypothesized exposure to acute IH would increase muscle sympathetic nerve activity (MSNA) via an increase in action potential (AP) discharge rates and within-burst firing. We further hypothesized any change in discharge patterns would be attenuated during acute chemoreceptor deactivation (hyperoxia). MSNA (microneurography) was assessed in 17 healthy adults (11 male/6 female; 31 ± 1 yr) during normoxic rest before and after 30 min of experimental IH. Prior to and following IH, participants were exposed to 2 min of 100% oxygen (hyperoxia). AP patterns were studied from the filtered raw MSNA signal using wavelet-based methodology. Compared with baseline, multiunit MSNA burst incidence (P < 0.01), AP incidence (P = 0.01), and AP content per burst (P = 0.01) were increased following IH. There was an increase in the probability of a particular AP cluster firing once (P < 0.01) and more than once (P = 0.03) per burst following IH. There was no effect of hyperoxia on multiunit MSNA at baseline or following IH (P > 0.05); however, hyperoxia following IH attenuated the probability of particular AP clusters firing more than once per burst (P < 0.01). Acute IH increases MSNA by increasing AP discharge rates and within-burst firing. A portion of the increase in within-burst firing following IH can be attributed to the carotid chemoreceptors. These data advance the mechanistic understanding of sympathetic activation following acute IH in humans.


Assuntos
Corpo Carotídeo/fisiopatologia , Hipóxia/fisiopatologia , Contração Muscular , Músculo Esquelético/inervação , Oxigênio/sangue , Recrutamento Neurofisiológico , Sistema Nervoso Simpático/fisiopatologia , Potenciais de Ação , Adulto , Biomarcadores/sangue , Corpo Carotídeo/metabolismo , Feminino , Humanos , Hipóxia/sangue , Hipóxia/diagnóstico , Masculino , Fatores de Tempo
19.
Life Sci ; 250: 117549, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179073

RESUMO

AIM: To evaluate physical fitness and cardiovascular effects in rats with renovascular hypertension, two kidneys, one clip (2K1C) submitted to voluntary exercise (ExV). MAIN METHODS: 24 h after surgery (SHAM and 2K1C) rats were submitted to ExV for one week (adaptation). ExV adherent rats were separated into exercise (2K1C-EX and SHAM-EX) or sedentary (2K1C-SED and SHAM-SED) groups. After 4 weeks, exhaustion test, plasma lactate, cardiovascular parameters were evaluated and gastrocnemius muscle was removed for evaluation of gene expression of muscle metabolism markers (PGC1α; AMPK, SIRT-1, UCP-3; MCP-1; LDH) and of the redox process. KEY FINDINGS: ExV decreased blood lactate concentration and increased SOD and CAT activity and a SIRT-1 and UCP-3 gene expression in the gastrocnemius muscle of 2K1C-ExV rats compared to 2K1C-SED rats. Gene expressions of PGC1α, UCP-3, MCT-1, AMPK were higher in 2K1C-ExV rats compared to SHAM-SED rats. Blood pressure in 2K1C-ExV was lower compared to 2K1C-SED and higher in SHAM-SED rats. Reflex bradycardia in 2K1C-EX rats increased compared to 2K1C-SED and was similar to SHAM-SED. The variation in mean blood pressure induced by ganglion blocker hexamethonium and Ang II AT1 receptor antagonist, losartan in the 2K1C-ExV rats was smaller compared to the 2K1C-SED rats and it was similar to the SHAM-SED rats. SIGNIFICANCE: O ExV induced adaptive responses in 2K1C-ExV rats by decreasing sympathetic and Ang II activities and stimulating intracellular signaling that favors redox balance and reduced blood lactate concentration. These adaptive responses, then, contribute to reduced arterial pressure, improved baroreflex sensitivity and physical fitness of 2K1C rats.


Assuntos
Hipertensão Renovascular/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Transdução de Sinais , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bradicardia , Modelos Animais de Doenças , Frequência Cardíaca/efeitos dos fármacos , Rim/efeitos dos fármacos , Losartan/farmacologia , Masculino , Oxirredução , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Endogâmicos F344 , Sirtuína 1/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Proteína Desacopladora 3/metabolismo
20.
Endocrinology ; 161(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32157301

RESUMO

Apolipoprotein A-IV (ApoA-IV) synthesized by the gut regulates lipid metabolism. Sympathetic innervation of adipose tissues also controls lipid metabolism. We hypothesized that ApoA-IV required sympathetic innervation to increase fatty acid (FA) uptake by adipose tissues and brown adipose tissue (BAT) thermogenesis. After 3 weeks feeding of either a standard chow diet or a high-fat diet (HFD), mice with unilateral denervation of adipose tissues received intraperitoneal administration of recombinant ApoA-IV protein and intravenous infusion of lipid mixture with radioactive triolein. In chow-fed mice, ApoA-IV administration increased FA uptake by intact BAT but not the contralateral denervated BAT or intact white adipose tissue (WAT). Immunoblots showed that, in chow-fed mice, ApoA-IV increased expression of lipoprotein lipase and tyrosine hydroxylase in both intact BAT and inguinal WAT (IWAT), while ApoA-IV enhanced protein levels of ß3 adrenergic receptor, adipose triglyceride lipase, and uncoupling protein 1 in the intact BAT only. In HFD-fed mice, ApoA-IV elevated FA uptake by intact epididymal WAT (EWAT) but not intact BAT or IWAT. ApoA-IV increased sympathetic activity assessed by norepinephrine turnover (NETO) rate in BAT and EWAT of chow-fed mice, whereas it elevated NETO only in EWAT of HFD-fed mice. These observations suggest that, in chow-fed mice, ApoA-IV activates sympathetic activity of BAT and increases FA uptake by BAT via innervation, while in HFD-fed mice, ApoA-IV stimulates sympathetic activity of EWAT to shunt FAs into the EWAT.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Apolipoproteínas A/farmacologia , Ácidos Graxos/metabolismo , Sistema Nervoso Simpático/metabolismo , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Masculino , Camundongos , Norepinefrina/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos
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