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1.
Nat Commun ; 12(1): 105, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397973

RESUMO

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-ß resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with ß1 adrenergic receptor antagonist. Conversely, ß1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell ß1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of ß1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.


Assuntos
Regulação para Baixo , Interferon beta/metabolismo , Esclerose Múltipla/complicações , Degeneração Neural/complicações , Receptores Adrenérgicos beta 1/metabolismo , Transdução de Sinais , Estresse Psicológico/complicações , Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Biomarcadores/metabolismo , Encéfalo/imunologia , Encéfalo/patologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/patologia , Feminino , Complexo de Golgi/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Degeneração Neural/sangue , Degeneração Neural/imunologia , Degeneração Neural/patologia , Neurônios/metabolismo , Neurônios/patologia , Norepinefrina/sangue , Fenótipo , Índice de Gravidade de Doença , Regulação para Cima/efeitos dos fármacos
2.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514622

RESUMO

A 38-yearr-old man presented with erectile dysfunction and infertility. On examination, he was hypertensive and detected to have a left flank mass. Blood investigations were unremarkable except raised serum noradrenaline levels. Imaging revealed multiple well-defined fat-containing hypodense lesions in left suprarenal area with largest one measuring 14×16 cm, suggestive of left adrenal myelolipoma. Diagnostic dilemma was posed due to discordance between clinical, biochemical and imaging findings. Left adrenal mass resection was planned keeping the possibility of pheochromocytoma. However, histopathology revealed it to be adrenal myelolipoma. Hypertension was resolved in the postoperative period and serum noradrenaline levels were normalised. Final diagnosis of a secretary adrenal myelolipoma was made, which is an extremely rare entity.


Assuntos
Hipertensão/etiologia , Mielolipoma/complicações , Mielolipoma/patologia , Mielolipoma/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Diagnóstico Diferencial , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Humanos , Masculino , Mielolipoma/metabolismo , Norepinefrina/sangue , Feocromocitoma/diagnóstico , Período Pós-Operatório , Resultado do Tratamento
3.
Cochrane Database Syst Rev ; 12: CD004022, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33314019

RESUMO

BACKGROUND: Recent cohort studies show that salt intake below 6 g is associated with increased mortality. These findings have not changed public recommendations to lower salt intake below 6 g, which are based on assumed blood pressure (BP) effects and no side-effects. OBJECTIVES: To assess the effects of sodium reduction on BP, and on potential side-effects (hormones and lipids) SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to April 2018 and a top-up search in March 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. The top-up search articles are recorded under "awaiting assessment." SELECTION CRITERIA: Studies randomizing persons to low-sodium and high-sodium diets were included if they evaluated at least one of the outcome parameters (BP, renin, aldosterone, noradrenalin, adrenalin, cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride,. DATA COLLECTION AND ANALYSIS: Two review authors independently collected data, which were analysed with Review Manager 5.3. Certainty of evidence was assessed using GRADE. MAIN RESULTS: Since the first review in 2003 the number of included references has increased from 96 to 195 (174 were in white participants). As a previous study found different BP outcomes in black and white study populations, we stratified the BP outcomes by race. The effect of sodium reduction (from 203 to 65 mmol/day) on BP in white participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.14 mmHg (95% confidence interval (CI): -1.65 to -0.63), 5982 participants, 95 trials; DBP: MD + 0.01 mmHg (95% CI: -0.37 to 0.39), 6276 participants, 96 trials. Hypertension: SBP: MD -5.71 mmHg (95% CI: -6.67 to -4.74), 3998 participants,88 trials; DBP: MD -2.87 mmHg (95% CI: -3.41 to -2.32), 4032 participants, 89 trials (all high-quality evidence). The largest bias contrast across studies was recorded for the detection bias element. A comparison of detection bias low-risk studies versus high/unclear risk studies showed no differences. The effect of sodium reduction (from 195 to 66 mmol/day) on BP in black participants was as follows: Normal blood pressure: SBP: mean difference (MD) -4.02 mmHg (95% CI:-7.37 to -0.68); DBP: MD -2.01 mmHg (95% CI:-4.37, 0.35), 253 participants, 7 trials. Hypertension: SBP: MD -6.64 mmHg (95% CI:-9.00, -4.27); DBP: MD -2.91 mmHg (95% CI:-4.52, -1.30), 398 participants, 8 trials (low-quality evidence). The effect of sodium reduction (from 217 to 103 mmol/day) on BP in Asian participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.50 mmHg (95% CI: -3.09, 0.10); DBP: MD -1.06 mmHg (95% CI:-2.53 to 0.41), 950 participants, 5 trials. Hypertension: SBP: MD -7.75 mmHg (95% CI:-11.44, -4.07); DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15), 254 participants, 8 trials (moderate-low-quality evidence).   During sodium reduction renin increased 1.56 ng/mL/hour (95%CI:1.39, 1.73) in 2904 participants (82 trials); aldosterone increased 104 pg/mL (95%CI:88.4,119.7) in 2506 participants (66 trials); noradrenalin increased 62.3 pg/mL: (95%CI: 41.9, 82.8) in 878 participants (35 trials); adrenalin increased 7.55 pg/mL (95%CI: 0.85, 14.26) in 331 participants (15 trials); cholesterol increased 5.19 mg/dL (95%CI:2.1, 8.3) in 917 participants (27 trials); triglyceride increased 7.10 mg/dL (95%CI: 3.1,11.1) in 712 participants (20 trials); LDL tended to increase 2.46 mg/dl (95%CI: -1, 5.9) in 696 participants (18 trials); HDL was unchanged -0.3 mg/dl (95%CI: -1.66,1.05) in 738 participants (20 trials) (All high-quality evidence except the evidence for adrenalin). AUTHORS' CONCLUSIONS: In white participants, sodium reduction in accordance with the public recommendations resulted in mean arterial pressure (MAP) decrease of about 0.4 mmHg in participants with normal blood pressure and a MAP decrease of about 4 mmHg in participants with hypertension. Weak evidence indicated that these effects may be a little greater in black and Asian participants. The effects of sodium reduction on potential side effects (hormones and lipids) were more consistent than the effect on BP, especially in people with normal BP.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dieta Hipossódica , Hipertensão/dietoterapia , Cloreto de Sódio na Dieta/farmacologia , Grupo com Ancestrais do Continente Africano , Aldosterona/sangue , Grupo com Ancestrais do Continente Asiático , Viés , Catecolaminas/sangue , Colesterol/sangue , Intervalos de Confiança , Epinefrina/sangue , Grupo com Ancestrais do Continente Europeu , Humanos , Hipertensão/etnologia , Norepinefrina/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Recomendações Nutricionais , Renina/sangue , Triglicerídeos/sangue
4.
Vasc Health Risk Manag ; 16: 257-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753874

RESUMO

Purpose: Our study aimed at determining and comparing the mechanism of cardiovascular protection variables in moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) in patients with stable coronary heart disease (CHD) after coronary stenting. Participants and Methods: This experimental study used the same subject and cross-over design, involving eleven stable CHD patients after coronary stenting. These were randomly divided into two groups; MICT for 29 minutes at 50-60% heart rate reserve and HIIT with 4x4 minute intervals at 60-80% heart rate reserve, each followed by three minutes of active recovery at 40-50% heart rate reserve. These were conducted three times a week for two weeks. The participants' levels of adrenaline, noradrenaline, endothelial nitric oxide synthase (eNOS), extracellular superoxide dismutase (EC-SOD) activity assayed, and flow-mediated dilatation (FMD) were examined before and after treatments were completed. Results: The HIIT significantly increased the levels of noradrenaline and eNOS compared with MICT (p<0.05). Also, HIIT was better in maintaining EC-SOD activity and FMD compared with MICT (p<0.05). Through the noradrenalin pathway, HIIT had a direct and significant effect on eNOS and FMD (p<0.05) but MICT, through the noradrenaline pathways, had a direct and significant effect on eNOS (p<0.05), and through the EC-SOD activity pathways had a direct and significant effect on FMD (p<0.05). MICT reduced EC-SOD activity and also decreased the FMD value. Conclusion: HIIT is superior to MICT in increasing cardiovascular protection by increasing the concentrations of noradrenalin and eNOS, maintaining EC-SOD activity, and FMD in stable CHD patients after coronary stenting.


Assuntos
Doença das Coronárias/terapia , Treinamento Intervalado de Alta Intensidade , Intervenção Coronária Percutânea/instrumentação , Stents , Adulto , Biomarcadores/sangue , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/fisiopatologia , Estudos Cross-Over , Epinefrina/sangue , Tolerância ao Exercício , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/sangue , Norepinefrina/sangue , Intervenção Coronária Percutânea/efeitos adversos , Superóxido Dismutase/sangue , Fatores de Tempo , Resultado do Tratamento
5.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R255-R263, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32667834

RESUMO

Fetal conditions associated with placental insufficiency and intrauterine growth restriction (IUGR) chronically elevate plasma norepinephrine (NE) concentrations. Our objective was to evaluate the effects of chronically elevated NE on insulin-stimulated glucose metabolism in normally grown, non-IUGR fetal sheep, which are independent of other IUGR-related reductions in nutrients and oxygen availability. After surgical placement of catheters, near-term fetuses received either a saline (control) or NE intravenous infusion with controlled euglycemia. In NE fetuses, plasma NE concentrations were 5.5-fold greater than controls, and fetal euglycemia was maintained with a maternal insulin infusion. Insulin secretion was blunted in NE fetuses during an intravenous glucose tolerance test. Weight-specific fluxes for glucose were measured during a euinsulinemic-euglycemic clamp (EEC) and a hyperinsulinemic-euglycemic clamp (HEC). Plasma glucose and insulin concentrations were not different between groups within each clamp, but insulin concentrations increased 10-fold between the EEC and the HEC. During the EEC, rates of glucose uptake (umbilical uptake + exogenous infusion) and glucose utilization were 47% and 35% lower (P < 0.05) in NE fetuses compared with controls. During the HEC, rates of glucose uptake were 28% lower (P < 0.05) in NE fetuses than controls. Glucose production was undetectable in either group, and glucose oxidation was unaffected by the NE infusion. These findings indicate that chronic exposure to high plasma NE concentrations lowers rates of net glucose uptake in the fetus without affecting glucose oxidation rates or initiating endogenous glucose production. Lower fetal glucose uptake was independent of insulin, which indicates insulin resistance as a consequence of chronically elevated NE.


Assuntos
Glicemia/metabolismo , Feto/metabolismo , Norepinefrina/sangue , Insuficiência Placentária/metabolismo , Animais , Feminino , Retardo do Crescimento Fetal/metabolismo , Insulina/sangue , Resistência à Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Gravidez , Ovinos
6.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R106-R113, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32493036

RESUMO

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Dispepsia/fisiopatologia , Dispepsia/terapia , Eletroacupuntura , Gastropatias/terapia , Estresse Psicológico/complicações , Vias Aferentes/fisiopatologia , Animais , Animais Recém-Nascidos , Esvaziamento Gástrico , Iodoacetamida , Masculino , Norepinefrina/sangue , Proteínas Proto-Oncogênicas c-fos/biossíntese , Ratos , Ratos Sprague-Dawley , Restrição Física , Núcleo Solitário/metabolismo , Gastropatias/induzido quimicamente , Nervo Vago/fisiopatologia
7.
Toxicol Appl Pharmacol ; 394: 114953, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32165127

RESUMO

Exercise training is one of the major non-pharmacological treatments for hypertension. However, the central mechanism by which exercise training attenuates the hypertensive responses remains unclear. Irisin is a muscle-secreted cytokine derived from fibronectin type III domain containing 5 (FNDC5) that will be released into the circulation during exercise. We hypothesized that irisin may play a role in the blood pressure regulation by exercise. To examine the hypothesis, our study investigated the effect of irisin on hypertension and its central mechanism. The study was performed in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats. We found that intravenous injection of irisin effectively reduced blood pressure, plasma norepinephrine, paraventricular nucleus (PVN) levels of neuronal activation, oxidative stress and inflammation in SHRs. Moreover, irisin activated nuclear factor E2-related factor-2 (Nrf2) and restored the imbalance of neurotransmitters in the PVN. Our study also found PVN knockdown of Nrf2 abolished the protective effects of irisin on hypertension. These findings demonstrate irisin can improve hypertension via Nrf2-mediated antioxidant in the PVN.


Assuntos
Anti-Hipertensivos/farmacologia , Fibronectinas/farmacologia , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/sangue , Estresse Oxidativo/efeitos dos fármacos , Esforço Físico , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
8.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R781-R789, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32130024

RESUMO

Sleep loss contributes to the development of cardiovascular, metabolic, and neurological disorders by promoting a systemic proinflammatory phenotype. The neuroendocrine-immune mechanisms contributing to such pathologies are poorly understood. The sympathetic nervous system (SNS) regulates immunity and is often activated following sleep disturbances. The aims of this study were to determine 1) the effect of SNS inhibition on inflammatory responses to sleep fragmentation (SF) and 2) whether homeostasis can be restored after 1 wk of recovery sleep. We measured stress responses (norepinephrine and corticosterone), gene expression levels of pro- and anti-inflammatory cytokines in peripheral (heart, liver, and spleen) tissues, and protein levels of cytokines and chemokines in serum of female mice that were subjected to acute SF for 24 h, chronic SF for 8 wk, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were chemically sympathectomized with 6-hydroxydopamine (6-OHDA) or injected with vehicle. Both acute and chronic SF elevated mRNA and protein levels of cytokines in peripheral tissues. Changes in inflammatory responses mirrored stress-axes activation, with increased corticosterone and norepinephrine in SF mice. 6-OHDA treatment significantly alleviated SF-induced inflammation, thus providing evidence of SNS regulation of peripheral inflammation from SF. Effects of chronic SF were more severe than acute SF, and 1 wk of recovery from SF sufficiently alleviated peripheral inflammatory responses but not NE responses.


Assuntos
Inflamação/prevenção & controle , Privação do Sono/patologia , Simpatectomia Química , Animais , Cortisona/sangue , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Norepinefrina/sangue , Oxidopamina/toxicidade , Estresse Fisiológico , Simpatolíticos/toxicidade
9.
Circ Arrhythm Electrophysiol ; 13(4): e007614, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32189516

RESUMO

BACKGROUND: Heart rate variability (HRV) and pulse rate variability are indices of autonomic cardiac modulation. Increased pericardial fat is associated with worse cardiovascular outcomes. We hypothesized that progressive increases in pericardial fat volume and inflammation prospectively dampen HRV in hypercholesterolemic pigs. METHODS: WT (wild type) or PCSK9 (proprotein convertase subtilisin-like/kexin type-9) gain-of-function Ossabaw mini-pigs were studied in vivo before and after 3 and 6 months of a normal diet (WT-normal diet, n=4; PCSK9-normal diet, n=6) or high-fat diet (HFD; WT-HFD, n=3; PCSK9-HFD, n=6). The arterial pulse waveform was obtained from an arterial telemetry transmitter to analyze HRV indices, including SD (SD of all pulse-to-pulse intervals over a single 5-minute period), root mean square of successive differences, proportion >50 ms of normal-to-normal R-R intervals, and the calculated ratio of low-to-high frequency distributions (low-frequency power/high-frequency power). Pericardial fat volumes were evaluated using multidetector computed tomography and its inflammation by gene expression of TNF (tumor necrosis factor)-α. Plasma lipid panel and norepinephrine level were also measured. RESULTS: At diet completion, hypercholesterolemic PCSK9-HFD had significantly (P<0.05 versus baseline) depressed HRV (SD of all pulse-to-pulse intervals over a single 5-minute period, root mean square of successive differences, proportion >50 ms, high-frequency power, low-frequency power), and both HFD groups had higher sympathovagal balance (SD of all pulse-to-pulse intervals over a single 5-minute period/root mean square of successive differences, low-frequency power/high-frequency power) compared with normal diet. Pericardial fat volumes and LDL (low-density lipoprotein) cholesterol concentrations correlated inversely with HRV and directly with sympathovagal balance, while sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF-α expression was upregulated in PCSK9-HFD, colocalized with nerve fibers, and correlated inversely with root mean square of successive differences and proportion >50 ms. CONCLUSIONS: Progressive pericardial fat expansion and inflammation are associated with a fall in HRV in Ossabaw mini-pigs, implying aggravated autonomic imbalance. Hence, pericardial fat accumulation is associated with alterations in HRV and the autonomic nervous system. Visual Overview: A visual overview is available for this article.


Assuntos
Tecido Adiposo/fisiopatologia , Adiposidade , Arritmias Cardíacas/etiologia , Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca , Hipercolesterolemia/complicações , Inflamação/etiologia , Pericárdio/fisiopatologia , Tecido Adiposo/metabolismo , Animais , Animais Geneticamente Modificados , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Hipercolesterolemia/metabolismo , Hipercolesterolemia/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Masculino , Norepinefrina/sangue , Pericárdio/metabolismo , Suínos , Porco Miniatura/genética , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
10.
BMC Cardiovasc Disord ; 20(1): 60, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024466

RESUMO

BACKGROUND: Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incompletely understood. In this study, we investigated changes in the interleukin-6 (IL-6)-glycoprotein 130-signal transducer and activator of transcription 3 (STAT3) pathway in the PVN during acute MI and the effects of this pathway on ventricular stability. METHODS: Rats were divided into a control group, a MI group, a PVN-injected anti-IL-6 antibody group and a PVN-injected SC144 group to observe how IL-6 and its downstream glycoprotein 130-STAT3 pathway in the PVN affect ventricular stability. The left anterior descending coronary artery was ligated to induce MI. After that, an anti-IL-6 antibody and SC144 were injected into the PVNs of rats. All data are expressed as the mean ± SE and were analysed by ANOVA with a post hoc LSD test. p < 0.05 was considered to indicate statistical significance. RESULTS: After MI, the concentration of the inflammatory factor IL-6 increased, and its downstream glycoprotein 130-STAT3 pathway was activated in the PVN. After injection of MI rat PVNs with the anti-IL-6 antibody or glycoprotein 130 inhibitor (SC144), glutamate levels increased and γ-aminobutyric acid (GABA) levels decreased in the PVN. Plasma norepinephrine concentrations also increased after treatment, which increased the vulnerability to VA. CONCLUSIONS: In summary, IL-6 in the PVN exerts a protective effect in MI rats, and the glycoprotein 130-STAT3 pathway plays a key role in this process. We anticipate that our findings will provide new ideas for the prevention and treatment of arrhythmia after MI.


Assuntos
Receptor gp130 de Citocina/metabolismo , Frequência Cardíaca , Interleucina-6/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fator de Transcrição STAT3/metabolismo , Fibrilação Ventricular/prevenção & controle , Função Ventricular Esquerda , Potenciais de Ação , Animais , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Norepinefrina/sangue , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
11.
Basic Res Cardiol ; 115(2): 15, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932910

RESUMO

Myocardial ischemia-reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored. First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a "two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate sympathoexcitation, and a 45-min ligation of the left coronary artery to induce myocardial I/R injury. The effects of RDN on the mobilization of immune cells in mice following myocardial I/R injury were explored. We observed a strong association between SNS overactivation and myeloid cell excessive accumulation in patients. In animal experiments, there was a significant reduction in infarct size per area at risk in the denervated-I/R group when compared to that of the innervated-I/R group (39.2% versus 49.8%; p < 0.005), and RDN also improved the left ventricular ejection fraction by 20% after 1 week. Furthermore, the denervated-I/R group showed a decrease in the number of neutrophils and macrophages in the blood and the myocardium as reflected by immunohistochemical staining and flow cytometry analysis (p < 0.05); the decrease was associated with a significant reduction in the circulating production of IL-1, IL-6 and TNF-α (p < 0.05). In summary, our study reveals a novel link between the SNS activity and inflammatory response undergoing myocardium I/R injury and identifies RDN as a potential therapeutic strategy against myocardium I/R injury via preserving the spleen immune cells mobilization.


Assuntos
Inflamação/prevenção & controle , Rim/irrigação sanguínea , Células Mieloides/imunologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Artéria Renal/inervação , Baço/imunologia , Simpatectomia , Sistema Nervoso Simpático/cirurgia , Adulto , Idoso , Animais , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Células Mieloides/metabolismo , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Norepinefrina/sangue , Baço/metabolismo , Volume Sistólico , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Função Ventricular Esquerda
12.
J Endocrinol ; 244(3): 523-533, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31958316

RESUMO

A high sympathetic tone is observed in the development and maintenance of the polycystic ovary (PCO) phenotype in rats. Neosaxitoxin (NeoSTX) specifically blocks neuronal voltage-dependent Na+ channels, and we studied the capacity of NeoSTX administered into the ovary to block sympathetic nerves and PCO phenotype that is induced by estradiol valerate (EV). The toxin was administered with a minipump inserted into the bursal cavity using two protocols: (1) the same day as EV administration and (2) 30 days after EV to block the final step of cyst development and maintenance of the condition. We studied the estrous cycling activity, follicular morphology, steroid plasma levels, and norepinephrine concentration. NeoSTX administered together with EV decreased NA intraovarian levels that were induced by EV, increased the number of corpora lutea, decreased the number of follicular cyst found after EV administration, and decreased the previously increased testosterone plasma levels induced by the PCO phenotype. Estrous cycling activity also recovered. NeoSTX applied after 30 days of EV administration showed near recovery of ovary function, suggesting that there is a specific window in which follicular development could be protected from cystic development. In addition, plasma testosterone levels decreased while those of progesterone increased. Our data strongly suggest that chronic inhibition of sympathetic nerves by a locally applied long-lasting toxin is a new tool to manage the polycystic phenotype in the rat and could be applied to other mammals depending on sympathetic nerve activity.


Assuntos
Ovário/inervação , Síndrome do Ovário Policístico/prevenção & controle , Saxitoxina/análogos & derivados , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Dinoflagelados/química , Estradiol/sangue , Ciclo Estral , Estro/metabolismo , Feminino , Humanos , Norepinefrina/sangue , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Progesterona/sangue , Ratos , Ratos Sprague-Dawley , Saxitoxina/administração & dosagem , Sistema Nervoso Simpático/fisiopatologia
13.
Sci Rep ; 10(1): 565, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980638

RESUMO

We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7-10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 minutes) and was much greater than that observed in the extended release group, which occurred later (270 minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Nifedipino/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/uso terapêutico , Débito Cardíaco/efeitos dos fármacos , Doença da Artéria Coronariana/fisiopatologia , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/farmacocinética , Nifedipino/uso terapêutico , Norepinefrina/sangue , Sistema Nervoso Simpático/fisiopatologia
14.
Am J Physiol Heart Circ Physiol ; 318(1): H124-H134, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834836

RESUMO

Elabela (ELA) is a newly discovered peptide that acts as a novel endogenous ligand of angiotensin receptor-like 1 (APJ) receptor. This study was designed to evaluate the effects of ELA-21 in paraventricular nucleus (PVN) on blood pressure and sympathetic nerve activity in spontaneously hypertensive rats (SHR). Experiments were performed in male Wistar-Kyoto rats (WKY) and SHR. ELA expression was upregulated in PVN of SHR. PVN microinjection of ELA-21 increased renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine, and arginine vasopressin (AVP) levels in SHR. Intravenous injection of ELA-21 significantly decreased MAP and HR in both WKY and SHR, but only induced a slight decrease in RSNA. APJ antagonist F13A in PVN abolished the effects of ELA-21 on RSNA, MAP and HR. Intravenous infusion of both ganglionic blocker hexamethonium and AVP V1a receptor antagonist SR49059 caused significant reduction in the effects of ELA-21 on RSNA, MAP and HR in SHR, while combined administration of hexamethonium and SR49059 abolished the effects of ELA-21. ELA-21 microinjection stimulated Akt and p85α subunit of phosphatidylinositol 3-kinase (PI3K) phosphorylation in PVN, whereas PI3K inhibitor LY294002 or Akt inhibitor MK-2206 almost abolished the effects of ELA-21 on RSNA, MAP, and HR. Chronic PVN infusion of ELA-21 induced sympathetic activation, hypertension, and AVP release accompanied with cardiovascular remodeling in normotensive WKY. In conclusion, ELA-21 in PVN induces exacerbated pressor and sympathoexcitatory effects in hypertensive rats via PI3K-Akt pathway.NEW & NOTEWORTHY We demonstrated that PVN microinjection of ELA-21 increases sympathetic nerve activity and blood pressure, which can be abolished by pretreatment of APJ antagonist. This is the first demonstration that central ELA can induce hypertension. The pressor effects in PVN are mediated by both sympathetic activation and vasopressin release via PI3K-Akt pathway. Our data confirm that ELA is upregulated in the PVN of SHR and so may be involved in the pressor and sympathoexcitatory effects in hypertension.


Assuntos
Pressão Arterial/efeitos dos fármacos , Hipertensão/induzido quimicamente , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Hormônios Peptídicos/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Arginina Vasopressina/sangue , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Modelos Animais de Doenças , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Injeções Intravenosas , Masculino , Microinjeções , Norepinefrina/sangue , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Hormônios Peptídicos/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
15.
J Sports Med Phys Fitness ; 60(4): 643-649, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31818057

RESUMO

BACKGROUND: Beta-blockers are still frequently used in cardiovascular diseases but may negatively influence the exercise capacity. The aim of the study was to analyze the effect of beta-blockade on physical performance and plasma level of catecholamine during different forms of exercise. METHODS: Ten prehypertensive athletes (age: 25.1±2.5 years, BMI: 24.4±2.4 kg/m2) performed repeated incremental exercise and steady-state-tests without and with the cardioselective beta-blocker bisoprolol (5mg/day). The cardiopulmonary, metabolic and the catecholamine responses were monitored. RESULTS: Beta-blocker treatment had no effect on maximum power output (Pmax), lactate and the maximal oxygen uptake (VO2max) (Pmax: 269.0±41.5 vs. 269.0±41.5 W; lactate: 8.7±2.6 vs. 8.6±3.2 mmol/L and VO2max: 3110±482 vs. 3077±425 mL/min, respectively; P not significant). Epinephrine and norepinephrine showed a similar exponential increase to maximum load with and without beta-blockade (epinephrinemax 1.92±1.8 vs. 1.93±1.3 nmol/L; P not significant; norepinephrinemax 12.78±7.9 vs. 16.89±12.2 nmol/L; P not significant). Beta-blockade lowered heart rate (HR) and systolic blood pressure (SBP) at rest and under maximum load (ΔHRrest: 10.6±11.1 bpm, P<0.05, ΔHR-Max: 27.8±6.6 bpm, P<0.01; ΔSBPrest: 19.4±9.3 mmHg, P<0.05, ΔSBPmax: 17.7±15.3 mmHg, P<0.01). The maximum oxygen pulse was higher in the tests performed under beta-blockade (IET: ΔVO2/HR: 3.1±2.2 mL/beat, P<0.01; SST: ΔVO2/HR: 3.4±1.4 mL/beat, P<0.001). CONCLUSIONS: Despite beta blockade and resulting differences in cardiopulmonary regulation during the exercise tests, the maximal oxygen capacity and the catecholamine concentration was similar. Higher exercise intensities (>50% Pmax) are associated with a marked increase in plasma catecholamines, which are not influenced by treatment with bisoprolol 5 mg/day.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Desempenho Atlético , Bisoprolol/administração & dosagem , Catecolaminas/sangue , Adulto , Atletas/estatística & dados numéricos , Epinefrina/sangue , Exercício Físico , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Ácido Láctico/sangue , Masculino , Norepinefrina/sangue , Consumo de Oxigênio , Adulto Jovem
16.
Am Heart J ; 219: 9-20, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710844

RESUMO

OBJECTIVE: An increasingly recognized prognostic factor for out-of-hospital-cardiac-arrest (OHCA) patients is the ischemia-reperfusion injury after restored blood circulation. Endothelial injury is common in patients resuscitated from cardiac arrest and is associated with poor outcome. This study was designed to investigate if iloprost infusion, a prostacyclin analogue, reduces endothelial damage in OHCA patients. METHODS: 50 patients were randomized in a placebo controlled double-blinded trial and allocated 1:2 to 48-hours iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Endothelial biomarkers (soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), vascular endothelial cadherine (VEcad), nucleosomes) and sympathoadrenal activation (epinephrine/norepinephrine) from baseline to 48 and 96-hours were evaluated. RESULTS: Iloprost infusion did not influence endothelial biomarkers by the 48-hour endpoint. A rebound effect was observed with higher biomarker plasma values in the iloprost group (sTM p=0.02; Syndecan p=0.004; nucleosomes p<0.001; VEcad p<0.03) after 96-hours. There was a significant difference in 180-day mortality in favor of placebo. There was no difference regarding total adverse events between groups (p=0.73). Two patients were withdrawn in the iloprost group due to hypotension. CONCLUSIONS: The administration of low-dose iloprost (1ng/kg/min) to OHCA patients did not significantly influence endothelial biomarkers as measured by the 48- hour endpoint. A rebound effect was however observed in the 96-hour statistical model, with increasing endothelial biomarker levels after cessation of the iloprost-infusion.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Iloprosta/administração & dosagem , Parada Cardíaca Extra-Hospitalar/terapia , Síndrome Pós-Parada Cardíaca/tratamento farmacológico , Vasodilatadores/administração & dosagem , Idoso , Antígenos CD/sangue , Biomarcadores/sangue , Temperatura Corporal , Caderinas/sangue , Método Duplo-Cego , Selectina E/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Epinefrina/sangue , Feminino , Humanos , Iloprosta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Nucleossomos , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/mortalidade , Projetos Piloto , Síndrome Pós-Parada Cardíaca/sangue , Síndrome Pós-Parada Cardíaca/mortalidade , Solução Salina/administração & dosagem , Tamanho da Amostra , Sindecana-1/sangue , Tromboelastografia , Trombomodulina/sangue , Fatores de Tempo , Vasodilatadores/efeitos adversos
17.
Med Sci Sports Exerc ; 52(3): 627-636, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31609299

RESUMO

INTRODUCTION: The study evaluated the role of lifelong physical activity for leg vascular function in postmenopausal women (61 ± 1 yr). METHOD: The study design was cross-sectional with three different groups based on self-reported physical activity level with regard to intensity and volume over the past decade: inactive (n = 14), moderately active (n = 12), and very active (n = 15). Endothelial-dependent and smooth muscle-dependent leg vascular function were assessed by ultrasound Doppler measurements of the femoral artery during infusion of acetylcholine (Ach), the nitric oxide (NO) donor sodium nitroprusside and the prostacyclin analog epoprostenol. Thigh muscle biopsies, arterial and venous plasma samples were obtained for assessment of vasodilator systems. RESULTS: The very active group was found to have 76% greater responsiveness to Ach compared with the sedentary group accompanied by 200% higher prostacyclin synthesis during Ach infusion. Smooth muscle cell responsiveness to sodium nitroprusside and epoprostenol was not different between groups. The protein amount of endothelial NO synthase and endogenous antioxidant enzymes in muscle tissue was higher in the very active than the inactive group. The moderately active group had a similar endothelial and smooth muscle cell responsiveness as the inactive group. A secondary comparison with a smaller group (n = 5) of habitually active young (24 ± 2 yr) women indicated that smooth muscle cell responsiveness and endothelial responsiveness are affected by age per se. CONCLUSIONS: This study shows that leg vascular function and the potential to form prostacyclin and NO in late postmenopausal women, is influenced by the extent of lifelong physical activity.


Assuntos
Endotélio Vascular/fisiologia , Exercício Físico/fisiologia , Perna (Membro)/irrigação sanguínea , Músculo Liso Vascular/fisiologia , Pós-Menopausa/fisiologia , 6-Cetoprostaglandina F1 alfa/sangue , Acetilcolina/farmacologia , Idoso , Estudos Transversais , Epoprostenol/farmacologia , Feminino , Artéria Femoral/fisiologia , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Músculo Liso Vascular/efeitos dos fármacos , Nitroprussiato/farmacologia , Norepinefrina/sangue , Fluxo Sanguíneo Regional , Vasodilatadores/farmacologia
18.
Stress ; 23(1): 87-96, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311393

RESUMO

Psychological stress may be linked to cancer incidence; however, more direct evidence is required to support this viewpoint. In this study, we investigated the effects of stress on immunosurveillance against cancer cells using a previously established examination stress model. We showed that the cancer killing activity (CKA) of granulocytes (also known as polymorphic nuclear cells, PMNs) is sharply reduced during examination stress stimulation in some donors who are psychologically sensitive to examination stress, with the concentration of plasma stress hormones (cortisone, epinephrine, and norepinephrine) increasing accordingly. The effects of stress hormones on immune cell CKA were also investigated under two in vitro co-incubation conditions, with all three hormones found to exert inhibitory effects on the CKA of PMNs and mononuclear cells. We showed that stress triggered the release of stress hormones which had profound inhibitory effects on the innate anticancer functions of PMNs. These results provide a possible explanation for the relationship between psychological stress and cancer incidence.


Assuntos
Granulócitos/fisiologia , Neoplasias/fisiopatologia , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Epinefrina/sangue , Epinefrina/fisiologia , Humanos , Hidrocortisona/sangue , Hidrocortisona/fisiologia , Norepinefrina/sangue , Norepinefrina/fisiologia
19.
J Pharm Biomed Anal ; 177: 112859, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31522098

RESUMO

Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC-MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [(S)-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0-500 ng/mL for epinephrine enantiomers and 1.5-750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l-epinephrine and l-norepinephrine were sensitively and accurately quantified while both the d-enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.


Assuntos
Epinefrina/farmacocinética , Norepinefrina/farmacocinética , Simpatomiméticos/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão/métodos , Epinefrina/administração & dosagem , Epinefrina/sangue , Epinefrina/química , Masculino , Modelos Animais , Estrutura Molecular , Norepinefrina/administração & dosagem , Norepinefrina/sangue , Norepinefrina/química , Ratos , Ratos Wistar , Organismos Livres de Patógenos Específicos , Estereoisomerismo , Relação Estrutura-Atividade , Simpatomiméticos/administração & dosagem , Simpatomiméticos/sangue , Simpatomiméticos/química , Espectrometria de Massas em Tandem/métodos
20.
PLoS One ; 14(11): e0224674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682617

RESUMO

Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Carvedilol/administração & dosagem , Insulina/metabolismo , Norepinefrina/metabolismo , Obesidade/tratamento farmacológico , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Administração Oral , Adrenérgicos , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Leptina/sangue , Leptina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Norepinefrina/sangue , Obesidade/etiologia , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos
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