RESUMO
The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.
Assuntos
Neurônios Adrenérgicos/citologia , Células Endoteliais/citologia , Endotélio Vascular/citologia , Células-Tronco Neurais/citologia , Neurogênese , Fibras Simpáticas Pós-Ganglionares/citologia , Neurônios Adrenérgicos/metabolismo , Animais , Aorta/citologia , Aorta/embriologia , Células Endoteliais/metabolismo , Endotélio Vascular/embriologia , Células-Tronco Neurais/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Fibras Simpáticas Pós-Ganglionares/embriologia , Peixe-ZebraRESUMO
OBJECTIVES: Fibromyalgia (FM) is a syndrome characterised by chronic musculoskeletal pain, hyperalgesia on specific areas of tenderness (tender points) and by an autonomic nervous system dysfunction consistent with sympathetic overactivity. It is not known whether there is any relationship between the amount of cardiovascular sympathetic activity and the magnitude of pain. Our objective was to assess this potential relationship in patients with FM. METHODS: Electrocardiogram, finger blood pressure, respiration and post-ganglionic sympathetic discharge activity (muscle sympathetic nerve activity, MSNA) were continuously recorded at rest in 25 patients with primary FMS. The autonomic profile was assessed by MSNA and spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation and of sympathetic vasomotor control (LF-SAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Cardiac baroreflex function was evaluated by the index α (αLF). Baroreceptor modulation of the sympathetic vasomotor control (sBRS) was assessed by the MSNA/diastolic pressure relationship. RESULTS: Pain intensity was linearly correlated with LFRR/HFRR (r² = 0.21; p=0.03), LFSAP (r² = 0.26; p=0.02) and MSNA (burst rate) (r² = 0.45; p=0.003). Pain intensity was inversely correlated with the αLF index (r² = 0.24; p=0.02) and the sBRS (r² = 0.28; p=0.03). Thus, the higher the sympathetic drive to the heart and vessels, the higher the magnitude of chronic pain. Also, the gains of both the cardiac and MSNA baroreceptor control were inversely related to the pain intensity. CONCLUSIONS: These findings raise the theoretical possibility that in FM patients the use of anti-adrenergic agents might lessen chronic pain intensity by reducing the underlying excessive sympathetic activity.
Assuntos
Sistema Cardiovascular/inervação , Dor Crônica/diagnóstico , Fibromialgia/diagnóstico , Pulmão/inervação , Músculo Esquelético/inervação , Percepção da Dor , Limiar da Dor , Sistema Nervoso Simpático/fisiopatologia , Adulto , Barorreflexo , Pressão Sanguínea , Determinação da Pressão Arterial , Dor Crônica/etiologia , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Eletrocardiografia , Eletromiografia , Feminino , Fibromialgia/complicações , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Frequência Cardíaca , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Valor Preditivo dos Testes , Taxa Respiratória , Índice de Gravidade de Doença , Fibras Simpáticas Pós-Ganglionares/fisiopatologiaRESUMO
Current evidence indicates that rises in systemic levels of estrogen create in the uterus an inhibitory environment for sympathetic nerves. However, molecular insights of these changes are far from complete. We evaluated if semaphorin 3F mRNA, a sympathetic nerve repellent, was produced by the rat uterus and if its expression was modulated by estrogen. We also analyzed whether uterine nerves express the semaphorin 3F binding receptor, neuropilin-2. Uterine levels of semaphorin 3F mRNA were measured using real time reverse transcriptase-polymerase chain reaction in prepubertal rat controls and following chronic estrogen treatment. Localization of semaphorin 3F transcripts was determined by in situ hybridization and the expression of neuropilin-2 was assessed by immunohistochemistry. These studies showed that: (1) chronic estrogen treatment led to a 5-fold induction of semaphorin 3F mRNA in the immature uterus; (2) estrogen provoked a tissue-specific induction of semaphorin 3F which was particularly localized in the connective tissue that borders muscle bundles and surrounds intrauterine blood vessels; (3) two major cell-types were recognized in the areas where transcripts were concentrated, fibroblast-like cells and infiltrating eosinophil leukocytes; and (4) some delicate nerve terminal profiles present in the estrogenized uterus were immunoreactive for neuropilin-2. Temporal and spatial expression patterns of semaphorin 3F/neuropilin-2 are consistent with a possible role of this guidance cue in the remodeling of uterine sympathetic innervation by estrogen. Though correlative in its nature, these data support a model whereby semaphorin 3F, in combination with other inhibitory molecules, converts the estrogenized myometrium to an inhospitable environment for sympathetic nerves.
Assuntos
Estrogênios/fisiologia , Miométrio/inervação , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Proteínas do Tecido Nervoso/biossíntese , Fibras Simpáticas Pós-Ganglionares/metabolismo , Regulação para Cima/fisiologia , Útero/inervação , Animais , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/agonistas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Miométrio/fisiologia , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Wistar , Útero/fisiologiaRESUMO
AIMS: To verify whether spectral components of atrial electrograms (AE) during sinus rhythm (SR) correlate with cardiac ganglionated plexus (GP) sites. METHODS AND RESULTS: Thirteen patients undergoing atrial fibrillation (AF) ablation were prospectively enrolled. Prior to radio frequency application, endocardial AE were recorded with a sequential point-by-point approach. Electrical stimuli were delivered at 20 Hz, amplitude 100 V, and pulse width of 4 ms. A vagal response was defined as a high-frequency stimulation (HFS) evoked atrioventricular block or a prolongation of RR interval. Spectral analysis was performed on single AE during SR, sampling rate of 1000 Hz, Hanning window. Overall, 1488 SR electrograms were analysed from 186 different left atrium sites, 129 of them corresponding to negative vagal response sites, and 57 to positive response sites. The electrogram duration and the number of deflections were similar in positive and negative response sites. Spectral power density of sites with vagal response was lower between 26 and 83 Hz and higher between 107 and 200 Hz compared with negative response sites. The area between 120 and 170 Hz normalized to the total spectrum area was tested as a diagnostic parameter. Receiver operating characteristic curve analysis demonstrated that an area 120-170/area(total) value >0.14 identified vagal sites with 70.9% sensitivity and 72.1% specificity. CONCLUSION: Spectral analysis of AE during SR in sites that correspond to the anatomical location of the GP is feasible and may be a simpler method of mapping the cardiac autonomic nervous system, compared with the HFS technique.
Assuntos
Fibrilação Atrial/fisiopatologia , Função Atrial/fisiologia , Técnicas Eletrofisiológicas Cardíacas/métodos , Gânglios Parassimpáticos/fisiologia , Nó Sinoatrial/fisiologia , Adulto , Fibrilação Atrial/cirurgia , Ablação por Cateter , Estimulação Elétrica/métodos , Feminino , Gânglios Parassimpáticos/cirurgia , Átrios do Coração/inervação , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nó Sinoatrial/inervação , Fibras Simpáticas Pós-Ganglionares/fisiologia , Nervo Vago/fisiologiaRESUMO
Neurons in the dorsomedial hypothalamus (DMH) play a key role in mediating tachycardia elicited by emotional stress. DMH activation by microinjections of the GABA(A) antagonist evokes tachycardia and physiological changes typically seen in experimental stress. DMH inhibition abolishes the tachycardia evoked by stress. Based on anatomic evidences for lateralization in the pathways from DMH, we investigated a possible inter-hemispheric difference in DMH-evoked cardiovascular responses. In anesthetized rats we compared changes in heart rate (HR), renal sympathetic activity (RSNA), mesenteric blood flow (MBF) and tail vascular conductance produced by activation of right (R) and left (L) sides of the DMH. We also evaluated the tachycardia produced by air jet stress after inhibition of R or L DMH. There were always greater increases in RSNA when bicuculline was injected ipsilaterally to the side where these parameters were recorded (average DeltaRSNA: L=+50% and R=+26%; P<0.05). Compared to pre-injection values, right DMH activation caused pronounced decrease (0.87+/-0.1% vs. 0.4+/-0.11%/mm Hg; P<0.05), whereas bicuculline methiodide (BMI) into left DMH produced no significant changes (0.95+/-0.09% vs. 1.04+/-0.25%/mm Hg) in tail vascular conductance. R or L DMH disinhibition produced decreases in MBF, but no differences in the range of these changes were observed. Activation of the right DMH caused greater tachycardia compared to the left DMH activation (average DeltaHR: R=+92 bpm; L=+48 bpm; P<0.05). Tachycardia evoked by air jet stress was smallest after right DMH inhibition (average DeltaHR: R=+57 bpm and L=+134 bpm; P<0.05). These results indicate that the descending cardiovascular pathways from DMH are predominantly lateralized and the right DMH might exert a prominent control on heart rate changes during emotional stress.
Assuntos
Vias Autônomas/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Núcleo Hipotalâmico Dorsomedial/fisiologia , Vias Eferentes/fisiologia , Lateralidade Funcional/fisiologia , Animais , Vias Autônomas/citologia , Vias Autônomas/efeitos dos fármacos , Bicuculina/farmacologia , Núcleo Hipotalâmico Dorsomedial/citologia , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Vias Eferentes/citologia , Vias Eferentes/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Frequência Cardíaca/fisiologia , Masculino , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/fisiologia , Circulação Esplâncnica/fisiologia , Estresse Psicológico/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/anatomia & histologia , Fibras Simpáticas Pós-Ganglionares/fisiologia , Sistema Nervoso Simpático/anatomia & histologia , Sistema Nervoso Simpático/fisiologia , Taquicardia/fisiopatologiaRESUMO
In this study the main question investigated was the number and size of both binucleate and mononucleate superior cervical ganglion (SCG) neurons and, whether post-natal development would affect these parameters. Twenty left SCGs from 20 male pacas were used. Four different ages were investigated, that is newborn (4 days), young (45 days), adult (2 years), and aged animals (7 years). By using design-based stereological methods, that is the Cavalieri principle and a physical disector combined with serial sectioning, the total volume of ganglion and total number of mononucleate and binucleate neurons were estimated. Furthermore, the mean perikaryal (somal) volume of mononucleate and binucleate neurons was estimated using the vertical nucleator. The main findings of this study were a 154% increase in the SCG volume, a 95% increase in the total number of mononucleate SCG neurons and a 50% increase in the total volume of SCG neurons. In conclusion, apart from neuron number, different adaptive mechanisms may coexist in the autonomic nervous system to guarantee a functional homeostasis during ageing, which is not always associated with neuron losses.
Assuntos
Envelhecimento/fisiologia , Neurônios/citologia , Roedores/anatomia & histologia , Roedores/crescimento & desenvolvimento , Gânglio Cervical Superior/citologia , Gânglio Cervical Superior/crescimento & desenvolvimento , Animais , Vias Autônomas/citologia , Vias Autônomas/crescimento & desenvolvimento , Fenômenos Fisiológicos Cardiovasculares , Contagem de Células , Núcleo Celular/fisiologia , Núcleo Celular/ultraestrutura , Proliferação de Células , Tamanho Celular , Lateralidade Funcional/fisiologia , Masculino , Neurogênese/fisiologia , Especificidade da Espécie , Fibras Simpáticas Pós-Ganglionares/citologia , Fibras Simpáticas Pós-Ganglionares/crescimento & desenvolvimentoRESUMO
Adaptive supersensitivity is a phenomenon characteristic of excitable tissues and discloses as a compensatory adjustment of tissue's response to unrelated stimulatory endogenous and exogenous substances after chronic interruption of excitatory neurotransmission. The mechanisms underlying such higher postjunctional sensitivity have been postulated for a variety of cell types. In smooth muscles, especially the vas deferens with its rich sympathetic innervation, the mechanisms responsible for supersensitivity are partly understood and appear to be different from one species to another. The present review provides a general understanding of adaptive supersensitivity and emphasizes early and recent information about the putative mechanisms involved in this phenomenon in rodent vas deferens.
Assuntos
Adaptação Fisiológica , Plexo Hipogástrico/fisiologia , Transdução de Sinais/fisiologia , Fibras Simpáticas Pós-Ganglionares/fisiologia , Ducto Deferente/fisiologia , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Sinalização do Cálcio , Cobaias , Humanos , Plexo Hipogástrico/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Ratos , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Adrenérgicos/fisiologia , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Transdução de Sinais/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/fisiologia , Simpatectomia , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Fatores de Tempo , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/inervaçãoRESUMO
BACKGROUND: Previous studies have associated neurohumoral excitation, as estimated by plasma norepinephrine levels, with increased mortality in heart failure. However, the prognostic value of neurovascular interplay in heart failure (HF) is unknown. We tested the hypothesis that the muscle sympathetic nerve activity (MSNA) and forearm blood flow would predict mortality in chronic heart failure patients. METHODS: One hundred and twenty two heart failure patients, NYHA II-IV, age 50+/-1 ys, LVEF 33+/-1%, and LVDD 7.1+/-0.2 mm, were followed up for one year. MSNA was directly measured from the peroneal nerve by microneurography. Forearm blood flow was obtained by venous occlusion plethysmography. The variables were analyzed by using univariate, stepwise multivariate Cox proportional hazards analysis, and Kaplan-Meier analysis. RESULTS: After one year, 34 pts died from cardiac death. The univariate analysis showed that MSNA, forearm blood flow, LVDD, LVEF, and heart rate were significant predictors of mortality. The multivariate analysis showed that only MSNA (P=0.001) and forearm blood flow (P=0.003) were significant independent predictors of mortality. On the basis of median levels of MSNA, survival rate was significantly lower in pts with >49 bursts/min. Similarly, survival rate was significantly lower in pts with forearm blood flow <1.87 ml/min/100 ml (P=0.002). CONCLUSION: MSNA and forearm blood flow predict mortality rate in patients with heart failure. It remains unknown whether therapies that specifically target these abnormalities will improve survival in heart failure.
Assuntos
Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Músculo Esquelético/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Feminino , Antebraço/irrigação sanguínea , Antebraço/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Taxa de Sobrevida/tendências , Sistema Nervoso Simpático/fisiopatologiaRESUMO
Functional asymmetry has been reported in sympathetic ganglia. Although there are few studies reporting on body side-related morphoquantitative changes in sympathetic ganglion neurons, none of them have used design-based stereological methods to address this issue during post-natal development. We therefore aimed at detecting possible asymmetry-related effects on the quantitative structure of the superior cervical ganglion (SCG) from pacas during ageing, using very precise design-based stereological methods. Forty (twenty left and twenty right) SCG from twenty male pacas were studied at four different ages, i.e. newborn, young, adult and aged animals. By using design-based stereological methods the total volume of ganglion and the total number of mononucleate and binucleate neurons were estimated. Furthermore, the mean perikaryal volume of mononucleate and binucleate neurons was estimated, using the vertical nucleator. The main findings of this study were: (1) the right SCG from aged pacas has more mononucleate and binucleate neurons than the left SCG in all other combinations of body side and animal age, showing the effect of the interaction between asymmetry (right side) and animal age, and (2) right SCG neurons (mono and binucleate) are bigger than the left SCG neurons (mono and binucleate), irrespective of the animal age. This shows, therefore, the exclusive effect of asymmetry (right side). At the time of writing there is still no conclusive explanation for some SCG quantitative changes exclusively assigned to asymmetry (right side) and those assigned to the interaction between asymmetry (right side) and senescence in pacas. We therefore suggest that forthcoming studies should focus on the functional consequences of SCG structural asymmetry during post-natal development. Another interesting investigation would be to examine the interaction between ganglia and their innervation targets using anterograde and retrograde neurotracers. Would differences in the size of target organs explain ganglia structural asymmetry?
Assuntos
Envelhecimento/fisiologia , Neurogênese/fisiologia , Neurônios/citologia , Gânglio Cervical Superior/citologia , Gânglio Cervical Superior/crescimento & desenvolvimento , Fatores Etários , Animais , Vias Autônomas/citologia , Vias Autônomas/crescimento & desenvolvimento , Contagem de Células , Diferenciação Celular/fisiologia , Crescimento Celular , Núcleo Celular/fisiologia , Núcleo Celular/ultraestrutura , Lateralidade Funcional/fisiologia , Neurônios/fisiologia , Roedores/anatomia & histologia , Roedores/crescimento & desenvolvimento , Fibras Simpáticas Pós-Ganglionares/citologia , Fibras Simpáticas Pós-Ganglionares/crescimento & desenvolvimentoRESUMO
Aging is associated with a decline in immune function (immunosenescence), a condition known to correlate with increased incidence of cancer as well as infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. Circulating melatonin decreases with age, and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes and macrophages. It also stimulates the production of natural killer cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from natural killer cells and T helper lymphocytes are enhanced by melatonin. Melatonin has the potential therapeutic value to enhance immune function in aged individuals.
Assuntos
Envelhecimento/fisiologia , Sistema Imunitário/fisiologia , Melatonina/fisiologia , Neuroimunomodulação/fisiologia , Adjuvantes Imunológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ritmo Circadiano , Citocinas/fisiologia , Células Precursoras de Granulócitos/citologia , Células Precursoras de Granulócitos/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/fisiologia , Imunocompetência , Células Matadoras Naturais/metabolismo , Melatonina/deficiência , Melatonina/metabolismo , Melatonina/uso terapêutico , Glândula Pineal/metabolismo , Receptores de Melatonina/efeitos dos fármacos , Receptores de Melatonina/fisiologia , Taxa Secretória , Sono/fisiologia , Gânglio Cervical Superior/fisiologia , Fibras Simpáticas Pós-Ganglionares/fisiologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismoRESUMO
Several findings suggest that A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. Recently we demonstrated that the renal vasodilation induced by infusion of hypertonic saline (HS) depends on the integrity of the A1 neurons. Here we determined the effect of lesions of these neurons on the inhibition of the renal sympathetic nerve activity (RSNA) induced by HS infusion. All experiments were performed in Wistar rats (280-350 g). A1 neurons were lesioned by microinjections of antidopamine-beta-hydroxylase-saporin (6.3 ng in 60 nl) into the CVLM (n=5), whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n=10). Two weeks later, rats were anesthetized (urethane 1.2 g/kg, iv), and instrumented for recording of arterial pressure and RSNA. In sham rats, HS infusion (3 M NaCl, 0.18 ml/100 g bw, iv) induced a transient (
Assuntos
Hipernatremia/fisiopatologia , Bulbo/metabolismo , Inibição Neural/fisiologia , Neurônios/metabolismo , Norepinefrina/metabolismo , Artéria Renal/inervação , Fibras Simpáticas Pós-Ganglionares/fisiologia , Animais , Vias Autônomas/citologia , Vias Autônomas/metabolismo , Pressão Sanguínea/fisiologia , Vias Eferentes/citologia , Vias Eferentes/metabolismo , Hipotensão/fisiopatologia , Masculino , Bulbo/citologia , Ratos , Ratos Wistar , Artéria Renal/fisiologia , Formação Reticular/citologia , Formação Reticular/metabolismo , Solução Salina Hipertônica/farmacologia , Simpatectomia Química/métodos , Vasodilatação/fisiologia , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
We have recently demonstrated that s.c.-injected 5-hydroxytryptamine (5-HT) induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Although the mechanisms mediating hyperalgesia can be quite separate and distinct from those mediating nociception, the aim of this study was to test the hypothesis that 5-HT induces mechanical hyperalgesia by mechanisms similar to those mediating nociception. s.c. injection of 5-HT induced a dose-dependent mechanical hyperalgesia measured by the mechanical paw withdrawal nociceptive threshold test in the rat. 5-HT-induced hyperalgesia was significantly reduced by local blockade of the 5-HT(3) receptor by tropisetron, by the nonspecific selectin inhibitor fucoidan, by the cyclooxygenase inhibitor indomethacin, by guanethidine depletion of norepinephrine in the sympathetic terminals, and by local blockade of the beta(1)- or beta(2)-adrenergic receptor by atenolol or ICI 118,551, respectively. Taken together, these findings indicate that like nociception, hyperalgesia induced by the injection of 5-HT in the s.c. tissue is also mediated by an indirect action of 5-HT on the primary afferent nociceptor. This indirect hyperalgesic action of 5-HT is mediated by a combination of mechanisms involved in inflammation such as neutrophil migration and the local release of prostaglandin and norepinephrine. However, in contrast to nociception, hyperalgesia induced by 5-HT in the s.c. tissue is mediated by a norepinephrine-dependent mechanism that involves the activation of peripheral beta(2) adrenoceptors.
Assuntos
Vias Aferentes/metabolismo , Hiperalgesia/metabolismo , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo , Pele/inervação , Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas de Receptores Adrenérgicos beta 2 , Antagonistas Adrenérgicos beta/farmacologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiopatologia , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Relação Dose-Resposta a Droga , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Masculino , Nociceptores/efeitos dos fármacos , Nociceptores/fisiopatologia , Norepinefrina/metabolismo , Medição da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Prostaglandinas/metabolismo , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Selectinas/efeitos dos fármacos , Selectinas/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiopatologia , Serotonina/farmacologia , Antagonistas do Receptor 5-HT3 de Serotonina , Antagonistas da Serotonina/farmacologia , Pele/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Fibras Simpáticas Pós-Ganglionares/metabolismoRESUMO
The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.
Assuntos
Barorreflexo/fisiologia , Infarto do Miocárdio/fisiopatologia , Artéria Renal/inervação , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Hipotensão/fisiopatologia , Masculino , Ratos , Ratos Wistar , Renina/sangue , Serotonina/metabolismo , Serotonina/farmacologia , Taquicardia/fisiopatologiaRESUMO
Both clinical and experimental studies dealing with patients affected by idiopathic or essential hypertension (EH) are devoted to the great deal of physiological, pharmacological and pathological as well as therapeutical issues of EH. However, most articles devoted to EH do not refer to the central nervous system mechanisms underlying this disease and the channels which allow that these mechanisms are funneled to the peripheral autonomic nervous system and trigger this cardiovascular disorder. In the present review article we attempted to reach this target devoted to the central nervous system circuitry involved in the cardiovascular pathophysiology. We postulated that EH depends on the predominance of the binomial A5 noradrenergic (NA) nucleus + median raphe serotonergic (5-HT) nucleus over the (A6)-NA + dorsal raphe-5HT nuclei. This hypothesis receives additional support from our results obtained throughout the neuropharmacological therapy of this type of neurophysiological disorder. Our therapeutical strategy is addressed to enhance the activity of the (A6)-NA + dorsal raphe-5HT binomial circuitry.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Vias Autônomas/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Hipertensão/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Acetilcolina/fisiologia , Animais , Vias Autônomas/metabolismo , Sistema Nervoso Central/anatomia & histologia , Sistema Nervoso Central/metabolismo , Humanos , Norepinefrina/fisiologia , Núcleos da Rafe/metabolismo , Núcleos da Rafe/fisiopatologia , Serotonina/fisiologiaRESUMO
The innervation within mammalian kidneys (intrinsic innervation) has been extensively described in the literature, particularly for rats. In contrast, there is still a lack of detailed description of the morphology of the extrinsic renal nerves leading to the kidney. The aim of the present study was to describe, in detail, the morphology of the renal nerves in rats. Left renal nerves were evaluated in 6 normal adult Wistar rats. After nerve recordings, in order to ascertain that the nerves studied were the extrinsic renal nerves, rats were killed and the nerves prepared for transmission electron microscopy. Morphometry was carried out with the aid of computer software. The total numbers of myelinated and unmyelinated fibers were 22+/-6 and 1246+/-110, respectively, with a ratio of unmyelinated/myelinated fiber of 109+/-26. The diameters of myelinated fibers showed an unimodal distribution with a peak at 3.0 microm but more than 17% of the fibers showed diameters larger than 5 microm. Unmyelinated fiber distribution was unimodal, with peak between 0.5 and 0.7 microm. The present study adds new information on the morphology of renal nerves in rats and provides morphological basis for further studies involving the structural basis of altered renal responses in conditions such as hypertension, ageing, diabetes and peripheral neuropathies.
Assuntos
Rim/inervação , Fibras Simpáticas Pós-Ganglionares/ultraestrutura , Animais , Masculino , Microscopia Eletrônica de Transmissão , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Mielinizadas/ultraestrutura , Fibras Nervosas Amielínicas/fisiologia , Fibras Nervosas Amielínicas/ultraestrutura , Ratos , Ratos Wistar , Artéria Renal/inervação , Artéria Renal/fisiologia , Fibras Simpáticas Pós-Ganglionares/fisiologiaRESUMO
In rats, autonomic nerve endings are damaged during Trypanosoma cruzi-induced myocarditis. Gradual recovery occurs after the acute phase. The present work shows the cardiac levels of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), and their cellular sources during T. cruzi infection in rats. Atrial and ventricular NGF levels (ELISA) increased significantly at day 20 post inoculation, the time-point of maximal sympathetic denervation. ELISA failed to show significant increase of cardiac GDNF levels. However immunohistochemistry showed a significant increase of anti-GDNF gold particles over atrial granules at day 20. Light microscopy showed stronger NGF immunostaining in atrial cardiomyocytes and several blood capillaries. In situ hybridization showed NGF and GDNF mRNAs in atrial and ventricular myocytes of both infected and uninfected animals. Endothelial cells exhibited NGF mRNA and protein only in infected rats. No evidence of neurotrophic factor expression by the infiltrating mononuclear cells was found. This is the first report on neurotrophic factor expression during T. cruzi infection. Our findings indicate an important role for NGF in the regenerative phenomena subsequent to a myocarditis able to damage sympathetic nerve endings, with preservation of preterminals and nerve trunks. GDNF could have a minor or a more transient participation.
Assuntos
Cardiomiopatia Chagásica/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/biossíntese , Coração/inervação , Miocardite/metabolismo , Miocárdio/metabolismo , Degeneração Neural/patologia , Fator de Crescimento Neural/biossíntese , Regeneração Nervosa , Fibras Simpáticas Pós-Ganglionares/fisiologia , Animais , Convalescença , Progressão da Doença , Endotélio/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/fisiologia , Átrios do Coração/metabolismo , Ventrículos do Coração/metabolismo , Técnicas Imunoenzimáticas , Hibridização In Situ , Microscopia Imunoeletrônica , Miocardite/parasitologia , Miócitos Cardíacos/metabolismo , Degeneração Neural/metabolismo , Terminações Nervosas/metabolismo , Terminações Nervosas/patologia , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/fisiologia , RNA Mensageiro/biossíntese , Ratos , Fibras Simpáticas Pós-Ganglionares/patologiaRESUMO
Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and alpha-tubulin, while the same treatment did not affect the expression of the non-specific sympathetic markers Erk1 and Erk2, and glyceraldehyde-3-phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.
Assuntos
Melatonina/sangue , Glândula Pineal/metabolismo , Estresse Psicológico/sangue , Sistema Nervoso Simpático/metabolismo , Animais , Biomarcadores/metabolismo , Doença Crônica , Regulação para Baixo/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gliceraldeído 3-Fosfato/metabolismo , Imuno-Histoquímica , Masculino , Melatonina/metabolismo , Atividade Motora/fisiologia , Glândula Pineal/inervação , Ratos , Ratos Sprague-Dawley , Receptor de Fator de Crescimento Neural/metabolismo , Restrição Física , Estresse Psicológico/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/metabolismo , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Tubulina (Proteína)/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima/fisiologiaRESUMO
The pre-synaptic sympathetic modulator role of adenosine was assessed by studying transmitter release following electrical depolarization of nerve endings from the rat mesenteric artery. Mesentery perfusion with exogenous adenosine exclusively inhibited the release of norepinephrine (NA) but did not affect the overflow of neuropeptide Y (NPY), establishing the basis for a differential pre-synaptic modulator mechanism. Several adenosine structural analogs mimicked adenosine's effect on NA release and their relative order of potency was: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride = 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-d-ribofuranuronamide = 5'-(N-ethylcarboxamido)adenosine >> adenosine > N(6)-cyclopentyladenosine. The use of selective receptor subtype antagonists confirmed the involvement of A(2A) and A(3) adenosine receptors. The modulator role of adenosine is probably due to the activation of both receptors; co-application of 1 nM 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride plus 1 nM 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-D-ribofuranuronamide caused additive reductions in NA released. Furthermore, while 1 nM of an A(2A) or A(3) receptor antagonist only partially reduced the inhibitory action of adenosine, the combined co-application of the two antagonists fully blocked the adenosine-induced inhibition. Only the simultaneous blockade of the adenosine A(2A) plus A(3) receptors with selective antagonists elicited a significant increase in NA overflow. H 89 reduced the release of both NA and NPY. We conclude that pre-synaptic A(2A) and A(3) adenosine receptor activation modulates sympathetic co-transmission by exclusively inhibiting the release of NA without affecting immunoreactive (ir)-NPY and we suggest separate mechanisms for vesicular release modulation.
Assuntos
Neuropeptídeo Y/metabolismo , Norepinefrina/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptor A3 de Adenosina/metabolismo , Receptores A2 de Adenosina/metabolismo , Fibras Simpáticas Pós-Ganglionares/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Agonistas do Receptor A3 de Adenosina , Antagonistas do Receptor A3 de Adenosina , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Isoquinolinas/farmacologia , Masculino , Artérias Mesentéricas/inervação , Artérias Mesentéricas/fisiologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/metabolismoRESUMO
This article presents a review of the role of the sympathetic activity in ovarian pathologies affecting reproductive function. We provide a succinct outline of the findings of our group in this area. The participation of stress as an etiological factor for ovarian pathologies throughout animal models and data in patients with polycystic ovary syndrome give strong support for participation of sympathetic nerves in the ovary function both in normal and pathological status.
Assuntos
Ovário/inervação , Síndrome do Ovário Policístico/fisiopatologia , Receptores Adrenérgicos beta/fisiologia , Estresse Psicológico/complicações , Sistema Nervoso Simpático/fisiopatologia , Animais , Feminino , Haplorrinos , Humanos , Folículo Ovariano/inervação , Folículo Ovariano/fisiopatologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/etiologia , Ratos , Estresse Psicológico/fisiopatologia , Fibras Simpáticas Pós-Ganglionares/fisiopatologia , Sistema Nervoso Simpático/citologiaRESUMO
We prospectively performed neurophysiologic studies in nine Fabry's Disease (FD) patients (8 male and 1 female) in order to describe the results of nerve conduction studies (NCS) and electromyography (EMG) and to verify whether the sympathetic skin response (SSR) is impaired in these patients. The investigation protocol included SSR, sensory and motor NCS and EMG. SSR was performed not only in FD patients, but also in 18 normal controls. All FD patients had normal nerve conduction studies and electromyography. SSR was present in all controls with a mean amplitude of 1453.6+/-682.3 microV. However, the SSR was absent in six and lower than 500 microV in the remaining FD patients. All patients had normal sensory and motor NCS and EMG. SSR, on the other hand, was significantly altered in all patients and this test could, therefore, be useful in the diagnostic evaluation of FD patients.