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1.
Neuropathology ; 39(4): 259-267, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31074912

RESUMO

Acidosis is the most dangerous complication of subarachnoid hemorrhage (SAH). Although the carotid bodies (CBs) network is essential for pH regulation, neither binuclear neurons (BNN) nor their functions have been mentioned so far in the literature. The aim of this study was to investigate the crucial roles of mononuclear (MNN) or BNN in CBs on acidosis following SAH. Twenty-five hybrid rabbits were used. Five rabbits were used as a control group, six for sham, and the remaining 14 rabbits were used as the study group by injection of 1 mL of autologous arterial blood into the cisterna magna to produce SAH. Normal and degenerated MNN/BNN densities of CBs were counted by stereological methods. The mean blood pH values were: 7.362 ± 0.041 in the control group; 7.324 ± 0.064 in sham, 7.272 ± 0.062 in the SAH group. The degenerated MNN and BNN values were 5 ± 1/mm3 and 9 ± 3/mm3 in the control group; 15 ± 5/mm3 and 22 ± 6/mm3 in sham, 965 ± 113/mm3 and 1532 ± 176/mm3 in the SAH group. Mean pH values were under 7.212 ± 0.130 in animals with prominent degenerated BNN. The differences between MNN/pH changes were significant between the SAH and control groups (P < 0.005); whereas BNN/pH values were significant between the SAH and sham groups (pH < 0.005), SAH and control (P < 0.0001). BNN degeneration could result in more severe acidosis than MNN following SAH which has not been described so far.


Assuntos
Acidose/complicações , Corpo Carotídeo/metabolismo , Neurônios/metabolismo , Hemorragia Subaracnóidea/sangue , Animais , Corpo Carotídeo/patologia , Concentração de Íons de Hidrogênio , Neurônios/patologia , Coelhos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/patologia
2.
Respir Physiol Neurobiol ; 260: 70-81, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30439529

RESUMO

Chronic exposure to intermittent hyperoxia causes abnormal carotid body development and attenuates the hypoxic ventilatory response (HVR) in neonatal rats. We hypothesized that concurrent exposure to intermittent hypercapnic hypoxia would influence this plasticity. Newborn rats were exposed to alternating bouts of hypercapnic hypoxia (10% O2/6% CO2) and hyperoxia (30-40% O2) (5 cycles h-1, 24 h d-1) through 13-14 days of age; the experiment was run twice, once in a background of 21% O2 and once in a background of 30% O2 (i.e., "relative hyperoxia"). Hyperoxia had only small effects on carotid body development when combined with intermittent hypercapnic hypoxia: the carotid chemoafferent response to hypoxia was reduced, but this did not affect the HVR. In contrast, sustained exposure to 30% O2 reduced carotid chemoafferent activity and carotid body size which resulted in a blunted HVR. When given alone, chronic intermittent hypercapnic hypoxia increased carotid body size and reduced the hypercapnic ventilatory response but did not affect the HVR. Overall, it appears that intermittent hypercapnic hypoxia counteracted the effects of hyperoxia on the carotid body and prevented developmental plasticity of the HVR.


Assuntos
Hipercapnia/fisiopatologia , Hiperóxia/fisiopatologia , Ventilação Pulmonar/fisiologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Gasometria , Corpo Carotídeo/patologia , Corpo Carotídeo/fisiopatologia , Feminino , Hemoglobinas/metabolismo , Pulmão/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória , Fatores de Tempo
3.
Respir Physiol Neurobiol ; 259: 75-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30086385

RESUMO

The role of cystathionine-γ-lyase (CSE) derived H2S in the hypoxic and anoxic responses of the carotid body (CB) were examined. Experiments were performed on Sprague-Dawley rats, wild type and CSE knockout mice on C57BL/6 J background. Hypoxia (pO2 = 37 ± 3 mmHg) increased the CB sensory nerve activity and elevated H2S levels in rats. In contrast, anoxia (pO2 = 5 ± 4 mmHg) produced only a modest CB sensory excitation with no change in H2S levels. DL-propargylglycine (DL-PAG), a blocker of CSE, inhibited hypoxia but not anoxia-evoked CB sensory excitation and [Ca2+]i elevation of glomus cells. The inhibitory effects of DL-PAG on hypoxia were seen: a) when it is dissolved in saline but not in dimethyl sulfoxide (DMSO), and b) in glomus cells cultured for18 h but not in cells either soon after isolation or after prolonged culturing (72 h) requiring 1-3 h of incubation. On the other hand, anoxia-induced [Ca2+]i responses of glomus cell were blocked by high concentration of DL-PAG (300µM) either alone or in combination with aminooxyacetic acid (AOAA; 300µM) with a decreased cell viability. Anoxia produced a weak CB sensory excitation and robust [Ca2+]i elevation in glomus cells of both wild-type and CSE null mice. As compared to wild-type, CSE null mice exhibited impaired CB chemo reflex as evidenced by attenuated efferent phrenic nerve responses to brief hyperoxia (Dejours test), and hypoxia. Inhalation of 100% N2 (anoxia) depressed breathing in both CSE null and wild-type mice. These observations demonstrate that a) hypoxia and anoxia are not analogous stimuli for studying CB physiology and b) CSE-derived H2S contributes to CB response to hypoxia but not to that of anoxia.


Assuntos
Corpo Carotídeo/efeitos dos fármacos , Cistationina gama-Liase/metabolismo , Hipóxia/patologia , Sulfitos/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Corpo Carotídeo/patologia , Células Cultivadas , Cistationina gama-Liase/genética , Hipóxia/tratamento farmacológico , Masculino , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/fisiologia , Ratos , Ratos Sprague-Dawley , Sulfitos/farmacologia
4.
Xenotransplantation ; 25(6): e12410, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29932254

RESUMO

BACKGROUND: The use of long-term immunosuppressive treatments on neural transplantation has been controversial during the last decades. Although nowadays there is a consensus about the necessity of maintaining a permanent state of immunosuppression to preserve the survival of cerebral grafts, little is known about the effects that chronic immunosuppression produces both on the neurodegenerative process and on transplants function. METHODS: Here, we establish a new immunosuppressive protocol, based on the discontinuous administration of CsA (15 mg/kg; s.c.) and prednisone (20 mg/kg; s.c.), to produce long-term immunosuppression in mice. Using this treatment, we analyse the effects that long-term immunosuppression induces in a chronic 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) model of parkinsonism and on the neuroprotective and neurorestorative anti-parkinsonian actions exerted by rat carotid body (CB) xenografts. RESULTS: This protocol preserves the survival of rat CB xenotransplants maintaining the general wellness of the grafted mice. Although permanent immunosuppression does not prevent the MPTP-induced cell death of nigral neurons and the consequent degeneration of dopaminergic striatal innervation, allowing for its use as Parkinson's disease (PD) model, it reduces the microglial activation and slightly declines the striatal damage. Moreover, we reported that chronic administration of immunosuppressant drugs does not alter the neuroprotective and restorative anti-parkinsonian actions of rat CB xenografts into parkinsonian mice. CONCLUSIONS: This new immunosuppressive protocol provides a new murine model to assay the long-term effects of cerebral xenografts and offer a pharmacological alternative to the commonly used genetic immunodeficient mice, allowing the use of genetically modified mice as hosts. In addition, it will permit the experimental analysis of the effects produced by human CB xenografts in the chronic PD murine model, with the final aim of using CB allografts as an option of cell therapy in PD patients.


Assuntos
Corpo Carotídeo/patologia , Terapia Baseada em Transplante de Células e Tecidos , Xenoenxertos/efeitos dos fármacos , Imunossupressão , Transplante Heterólogo , Animais , Corpo Estriado/patologia , Modelos Animais de Doenças , Dopamina/metabolismo , Imunossupressão/métodos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia
5.
J Histochem Cytochem ; 66(10): 753-765, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29775122

RESUMO

Chronic intermittent hypoxia (CIH), main feature of obstructive sleep apnea, produces nitro-oxidative stress, which contributes to potentiate carotid body (CB) chemosensory discharges and sympathetic-adrenal-axis activity, leading to hypertension. The MnSOD enzymatic activity, a key enzyme on oxidative stress control, is reduced by superoxide-induced nitration. However, the effects of CIH-induced nitration on MnSOD enzymatic activity in the CB and adrenal gland are not known. We studied the effects of CIH on MnSOD protein and immunoreactive (MnSOD-ir) levels in the CB, adrenal gland and superior cervical ganglion (SCG), and on 3-nitrotyrosine (3-NT-ir), CuZnSOD (CuZnSOD-ir), MnSOD nitration, and its enzymatic activity in the CB and adrenal gland from male Sprague-Dawley rats exposed to CIH for 7 days. CIH increased 3-NT-ir in CB and adrenal gland, whereas MnSOD-ir increased in the CB and in adrenal cortex, but not in the whole adrenal medulla or SCG. CIH nitrated MnSOD in the CB and adrenal medulla, but its activity decreased in the adrenal gland. CuZnSOD-ir remained unchanged in both tissues. All changes observed were prevented by ascorbic acid treatment. Present results show that CIH for 7 days produced MnSOD nitration, but failed to reduce its activity in the CB, because of the increased protein level.


Assuntos
Glândulas Suprarrenais/metabolismo , Corpo Carotídeo/metabolismo , Hipóxia/metabolismo , Superóxido Dismutase/metabolismo , Tirosina/análogos & derivados , Glândulas Suprarrenais/patologia , Animais , Corpo Carotídeo/patologia , Hipóxia/patologia , Imuno-Histoquímica , Masculino , Estresse Nitrosativo , Estresse Oxidativo , Ratos Sprague-Dawley , Tirosina/análise , Tirosina/metabolismo
6.
Respir Physiol Neurobiol ; 254: 10-15, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29627490

RESUMO

It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA). The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (VrCB+lCB) was based on computed tomography angiography. Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of VrCB+lCB. The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of VrCB+lCB. In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS.


Assuntos
Corpo Carotídeo/diagnóstico por imagem , Citocromo P-450 CYP11B2/genética , Hipertensão Essencial/diagnóstico por imagem , Hipertensão Essencial/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Angiotensina/genética , Idoso , Corpo Carotídeo/patologia , Angiografia por Tomografia Computadorizada , Hipertensão Essencial/tratamento farmacológico , Feminino , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença , Humanos , Masculino , Tamanho do Órgão , Estudos Retrospectivos
8.
Cell Tissue Res ; 372(2): 427-431, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29470646

RESUMO

Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H2S production in the CB. Blockade of H2S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H2S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H2S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H2S. Inhibiting H2S synthesis prevented IH-evoked sympathetic activation and hypertension.


Assuntos
Corpo Carotídeo/metabolismo , Corpo Carotídeo/patologia , Gases/metabolismo , Hipóxia/metabolismo , Hipóxia/patologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Sulfeto de Hidrogênio/metabolismo
9.
Physiol Genomics ; 50(3): 208-214, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29373079

RESUMO

The carotid body is now looked at as a multipurpose sensor for blood gases, blood pH, and several hormones. The matter of glucose sensing by the carotid body has been debated for several years in the literature, and these days there is a consensus that carotid body activity is modified by metabolic factors that contribute to glucose homeostasis. However, the sensing ability for glucose is still being pondered: are the carotid bodies low glucose sensors or, in contrast, are they overresponsive in high-glucose conditions? Herein, we debate the glucose and insulin sensing capabilities of the carotid body as key early events in the overactivation of the carotid body, which is increasingly recognized as an important feature of metabolic diseases. Additionally, we dedicate a final section to discuss new outside-the-box therapies designed to decrease carotid body activity that may be used for treating metabolic diseases.


Assuntos
Corpo Carotídeo/metabolismo , Corpo Carotídeo/patologia , Resistência à Insulina , Animais , Humanos , Doenças Metabólicas/patologia , Sistema Nervoso Simpático/patologia
10.
Rev. guatemalteca cir ; 23(1): [56-66], ene-dic,2017.
Artigo em Espanhol | LILACS | ID: biblio-884888

RESUMO

Introducción: Los tumores del cuerpo carotideo son tumores infrecuentes, generalmente benignos y muy vascularizados, por lo que su resección es un reto para el cirujano. El objetivo de este estudio es realizar una caracterización epidemiológica de los pacientes con glomus carotideo operados en la Unidad de Cirugía Cardiovascular de Guatemala (UNICAR) Metodología: El estudio fue descriptvo retrospectivo analizando los registros clínicos de todos los pacientes sometidos a resección de glomus carotideo en UNICAR de enero de 2,002 a diciembre de 2,015. Resultados: Se documentaron 17 pacientes a quienes se les realizo resección de glomus en la unidad, de los cuales 1 expediente no fue posible analizar porque no se encontró en el archivo. El 93% de los pacientes fueron de sexo femenino lo cual está descrito que es el género más afectado. La altitud es característica de esta patología ya que el 93%, 15 de los 16 venían de una altura mayor de los 1,500 mts sobre el nivel del mar. No se pudo determinar la etnia como factor de riesgo ya que el 50% de los pacientes fueron de etnia indígena y el 50% de etnia ladina. Se obtuvo un caso de herencia familiar ya que tanto la abuela como la nieta presentaron glomus carotideo. Las biopsias que se documentaron fueron solamente en 5 pero pensamos que hay un subregistro ya que consultando con los especialistas estás pudieron haber sido más. Conclusiones: El Glomus Carotideo es una patología poco frecuente, sin embargo, debe ser tratado en unidades especializadas vasculares debido a su compleja resección y el importante riesgo de sangrado. En este estudio se logró caracterizar epidemiológicamente a los pacientes, coincidiendo con lo reportado en la literatura mundial.


Background: Carotid body tumors are uncommon, generally benign, hypervascular turmors; resection is a challenge for surgeons. The aim of this study is to characterize patents with carotid body tumors who underwent resection at the Cardiovascular Surgical Unit in Guatemala (UNICAR) Methods and Results: There were a total of 17 patents in this descriptve and retrospectve trial who underwent resection of carotid body tumor during 2002 to 2015, but we only had access to 16 of the patents clinical records. 93% were female patents, this is the same as reported in other trials being women more affected than men. Altitude of more than 1,500 m from sea level was present in 93% of the patents. This is remarkable due to the country's geography where there can be in some department's altitudes from 0 m at sea level to as high as 2,800 m. Their background in race speaking isn't related to the presence of this pathology, 50% were indigenous and 50% were ladinos. There was only one case of family related heritage where grandmother and granddaughter had a carotid body tumor resection. Previous biopsy was only recorded in 5 clinical records but we think this can be a sub registry due to the experience of some of the surgeons who said most of them had previous scars and it made the resection more difficult. Conclusions: Carotid body tumors are rare in presentation and they must be treated in a specialized vascular unit due to its complex resection and hemorrhage risk.


Assuntos
Humanos , Masculino , Feminino , Tumor do Corpo Carotídeo/cirurgia , Corpo Carotídeo/patologia , Estudos Epidemiológicos , Paragânglios Cromafins
11.
Respir Physiol Neurobiol ; 246: 98-106, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28851593

RESUMO

Cystathionine-γ-lyase (CSE) is a multifunctional enzyme, and hydrogen sulfide (H2S) is one of its products. CSE and H2S have recently been proposed to be critical signaling molecules in hypoxia-induced excitation of carotid body (CB) glomus cells and the chemosensory response. Because the role of H2S in arterial chemoreception is still debated, we further examined the role of CSE by studying the effects of hypoxia on TASK K+ channel activity, cell depolarization, [Ca2+]i and ventilation using CSE+/+ and CSE-/- mice. As predicted, hypoxia reduced TASK activity and depolarized glomus cells isolated from CSE+/+ mice. These effects of hypoxia were not significantly altered in glomus cells from CSE-/- mice. Basal [Ca2+]i and hypoxia-induced elevation of [Ca2+] were also not significantly different in glomus cells from CSE+/+ and CSE-/- mice. In whole-body plethysmography, hypoxia (10%O2) increased minute ventilation in both CSE+/+ and CSE-/- mice equally well, and no significant differences were found in either males or females when adjusted by body weight. Together, these results show that deletion of the CSE gene has no effects on hypoxia-induced changes in TASK, cell depolarization, [Ca2+]i and ventilation, and therefore do not support the idea that CSE/H2S signaling is important for CB chemoreceptor activity in mice.


Assuntos
Cálcio/metabolismo , Corpo Carotídeo/patologia , Cistationina gama-Liase/metabolismo , Hipóxia , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Ventilação , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Animais Geneticamente Modificados , Bicarbonatos/farmacologia , Células Quimiorreceptoras/efeitos dos fármacos , Células Quimiorreceptoras/fisiologia , Cistationina gama-Liase/genética , Modelos Animais de Doenças , Feminino , Sulfeto de Hidrogênio/metabolismo , Hipóxia/metabolismo , Hipóxia/patologia , Hipóxia/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/farmacologia , Cloreto de Potássio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Volume de Ventilação Pulmonar/efeitos dos fármacos , Volume de Ventilação Pulmonar/fisiologia
12.
World Neurosurg ; 104: 330-338, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28456740

RESUMO

OBJECTIVE: The chemoreceptor network, consisting of the glossopharyngeal nerve and carotid body (GPN-CB), is essential for the regulation of blood pH. Its ischemic insults after subarachnoid hemorrhage (SAH), which may contribute to acidosis, have not been investigated. METHODS: Twenty-three hybrid rabbits were used. They were divided into 3 groups: 5 as a control group, 5 as a sham group, and the remaining 13 as the study group. Injections included 1 cm3 serum saline and 1 cm3 autolog arterial blood into the cisterna magna in the sham and study group, respectively. Blood pH values of all animals were recorded. After 2 weeks, animals were euthanized. The number of normal and degenerated neurons of the carotid bodies (CBs) was counted by stereologic methods and analyzed statistically. RESULTS: Two of 13 rabbits died within the second week. The mean blood pH values were measured as 7.35 ± 0.07 in the control group (n = 5), 7.33 ± 0.06 in the sham group (n = 5), 7.29 ± 0.05 in rabbits with slight acidosis (n = 6), and 7.23 ± 0.02 in rabbits with prominent acidosis (n = 7). In the control group, the average normal neuronal density of the CBs was 6432 ± 790/mm3 and the degenerated neuron density was 11 ± 3/mm3, whereas the degenerated neuronal density in CBs was 35 ± 8/mm3 in the sham group and 1034 ± 112/mm3 in the slight acidosis-developed group (n = 6; P < 0.05). Conversely, degenerated neuron density of CBs was 2134 ± 251/mm3 in the prominent acidosis-developed animals (n = 7; P < 0.005). Interestingly, in the rabbits who died, the degenerated neuron density of the CB was 3160 ± 840/mm3. CONCLUSION: An inverse relationship between neurodegeneration in the CB and pH values secondary to the disruption of the GPN-CB network after SAH was found, which may contribute to developing acidosis.


Assuntos
Acidose/fisiopatologia , Análise Química do Sangue , Corpo Carotídeo/fisiopatologia , Modelos Animais de Doenças , Nervo Glossofaríngeo/fisiopatologia , Rede Nervosa/fisiopatologia , Hemorragia Subaracnóidea/fisiopatologia , Resultado do Tratamento , Acidose/patologia , Animais , Corpo Carotídeo/patologia , Nervo Glossofaríngeo/patologia , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Rede Nervosa/patologia , Coelhos , Hemorragia Subaracnóidea/patologia
13.
Auton Neurosci ; 205: 50-56, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28473232

RESUMO

The purpose of this study was to investigate immunoreactivity for dopamine ß-hydroxylase (DBH) and tyrosine hydroxylase (TH) in carotid body (CB) glomus cells in spontaneously hypertensive rats (SHR/Izm) at 4 (prehypertensive stage), 8 (early stage of developmental hypertension), 12 (later stage of developmental hypertension), and 16weeks of age (established hypertensive stage). Age-matched Wistar Kyoto rats (WKY/Izm) were used as controls. Staining properties for TH were similar between both strains at each age. Regarding DBH immunostaining, although some glomus cells showed intense DBH immunoreactivity at 4weeks of age, these cells were rarely observed at 8, 12, and 16weeks of age in WKY/Izm. In SHR/Izm, intense DBH immunoreactivity was observed in some glomus cells at 4weeks of age, these cells were also observed at 8 and 12weeks of age, and their number increased at 16weeks of age. An image analysis showed that the percentage of DBH-immunopositive glomus cells in WKY/Izm was approximately 30% at 4weeks of age and significantly decreased to approximately 10% at 8, 12, and 16weeks of age (p<0.05). This percentage in SHR/Izm was approximately 40% at each age. The gray scale intensity for DBH immunoreactivity in DBH-immunopositive glomus cells was similar in both strains at 4weeks of age, but became significantly lower in WKY/Izm and higher in SHR/Izm with increase in age (p<0.05). These results suggest that noradrenaline in glomus cells plays an important role in the regulation of neurotransmission between CB and afferent nerves during developmental hypertension.


Assuntos
Envelhecimento/metabolismo , Corpo Carotídeo/enzimologia , Dopamina beta-Hidroxilase/metabolismo , Hipertensão/enzimologia , Envelhecimento/patologia , Animais , Corpo Carotídeo/crescimento & desenvolvimento , Corpo Carotídeo/patologia , Contagem de Células , Imunofluorescência , Hipertensão/patologia , Masculino , Neurônios/enzimologia , Neurônios/patologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Tirosina 3-Mono-Oxigenase/metabolismo
15.
Respir Physiol Neurobiol ; 237: 22-34, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28034711

RESUMO

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2 (Control) or 60% O2 (Hyperoxia) until studied at 4, 6-7, or 13-14days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2 at all ages; CO2 sensitivity recovered within 7days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS.


Assuntos
Corpo Carotídeo/patologia , Células Quimiorreceptoras/fisiologia , Hipercapnia/fisiopatologia , Hiperóxia/fisiopatologia , Ventilação Pulmonar/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Potenciais de Ação/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Bicuculina/farmacologia , Dióxido de Carbono/farmacologia , Corpo Carotídeo/crescimento & desenvolvimento , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Hiperóxia/patologia , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Potenciais Sinápticos/efeitos dos fármacos , Potenciais Sinápticos/fisiologia
16.
Vascular ; 25(2): 184-189, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27357283

RESUMO

Background The study aims to conduct a review of the surgical management of carotid body tumor. Methods Consecutive patients with CBT who received surgical interventions from January 1994 to January 2014 at our institution were reviewed. Clinical, operative, pathological and follow up information were reported. Results Twenty patients (four males; median age was 36) with 21 CBT operations were recorded during the period. One patient undertook sequential operations for bilateral CBTs. Patients had 19 neck mass, 1 incidental finding and 1 facial nerve palsy. Six CBTs (28.6%) were Shamblin class I, ten (47.6%) were class II and five (23.8%) were class III. Nine CBTs had preoperative conjunctive embolization. Two operations required internal carotid artery resection and reconstruction. Four patients received subtotal resections, while 17 achieved complete resection. Complications included two major strokes, three hoarse voice and two Horner's syndrome. Shamblin class was significant predictor of operative time, blood loss, and whether complete resection accomplished, but could not predict postoperative complication. With median follow up period of 94 months, there was no tumor recurrence found in those had complete resection. Conclusions This small cohort showed that Shamblin class was significant in predicting technical difficulties but could not predict occurrence of complications.


Assuntos
Artérias Carótidas/cirurgia , Tumor do Corpo Carotídeo/cirurgia , Corpo Carotídeo/cirurgia , Procedimentos Cirúrgicos Vasculares , Adulto , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Corpo Carotídeo/diagnóstico por imagem , Corpo Carotídeo/patologia , Tumor do Corpo Carotídeo/classificação , Tumor do Corpo Carotídeo/diagnóstico por imagem , Tumor do Corpo Carotídeo/patologia , Angiografia por Tomografia Computadorizada , Bases de Dados Factuais , Embolização Terapêutica , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos , Estudos Retrospectivos , Fatores de Risco , Veia Safena/transplante , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/métodos , Adulto Jovem
17.
Respir Physiol Neurobiol ; 236: 5-10, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27989890

RESUMO

We tested the hypotheses that: (1) carotid body size can be measured by computed tomographic angiography (CTA) with high inter-observer agreement, and (2) patients with sleep apnea exhibit larger carotid bodies than those without sleep apnea. A chart review was conducted from patients who underwent neck CTA and polysomnography at the Mayo Clinic between January 2000 and February 2015. Widest axial measurements of the carotid bodies, performed independently by two radiologists, were possible in 81% of patients. Intra-class correlation coefficients ranged from 0.93 to 0.95 (Right carotid body: 0.93; Left: 0.94; Average: 0.95). Widest axial measurements of the carotid bodies were greater in patients with sleep apnea (n=32) compared to controls (n=46, P-value range 0.02-0.04). After adjusting for age, no differences in carotid body size were observed between the patient groups (P-value range 0.45-0.59). We conclude carotid body size can be detected by CTA with high inter-observer agreement; however, carotid body size is not increased in patients with sleep apnea.


Assuntos
Corpo Carotídeo/diagnóstico por imagem , Corpo Carotídeo/patologia , Síndromes da Apneia do Sono/patologia , Idoso , Pressão Sanguínea/fisiologia , Angiografia por Tomografia Computadorizada , Feminino , Lateralidade Funcional , Cabeça/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Polissonografia , Estudos Retrospectivos , Síndromes da Apneia do Sono/diagnóstico por imagem , Estatísticas não Paramétricas
18.
Clin Radiol ; 71(6): 616.e7-616.e13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27029889

RESUMO

AIM: To assess the relationship between the volume of the carotid bodies (VrCB+lCB) examined by means of computed tomography angiography (CTA) and blood pressure variability and pulse pressure (PP) in 24-hour ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. MATERIALS AND METHODS: A group of 52 patients with essential hypertension was examined (mean age: 68.32±12.31 years), the sizes of carotid bodies were measured by means of carotid artery CTA, and 24-hour ABPM was carried out. The 24-hour ABPM established systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), PP, SBP variability (SBPV), and DBP variability (DBPV). RESULTS: SBP, MAP, and SBPV were significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median, as well as in the group of hypertension patients with oversized carotid bodies, than in the group of hypertension patients with normal VrCB+lCB. Moreover, the PP was statistically significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median. The existence of statistically significant positive linear relationships was revealed between VrCB+lCB and SBP, PP, and SBPV. A higher body mass index, older age, smoking, and higher VrCB+lCB are independent risk factors increasing SBPV in the research group. CONCLUSION: A positive relationship between the size of the carotid bodies and variability of the SBP and PP is observed in patients with essential hypertension.


Assuntos
Pressão Sanguínea , Corpo Carotídeo/patologia , Corpo Carotídeo/fisiopatologia , Angiografia por Tomografia Computadorizada/métodos , Hipertensão/fisiopatologia , Idoso , Corpo Carotídeo/diagnóstico por imagem , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Imageamento Tridimensional/métodos , Masculino , Tamanho do Órgão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Oxid Med Cell Longev ; 2016: 9802136, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26798430

RESUMO

Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO(-)), a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO(-) scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB, the CB chemosensory discharge, and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u.), reduced CB chemosensory response to 5% O2 (266.5 ± 13.4 versus 168.6 ± 16.8 Hz), and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg). Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO(-) formation.


Assuntos
Corpo Carotídeo/patologia , Hipertensão/complicações , Hipóxia/complicações , Ácido Peroxinitroso/biossíntese , Animais , Azóis/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Corpo Carotídeo/efeitos dos fármacos , Corpo Carotídeo/fisiopatologia , Diástole/efeitos dos fármacos , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipóxia/patologia , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Ratos Sprague-Dawley , Sístole/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/metabolismo
20.
Respir Physiol Neurobiol ; 220: 69-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26444750

RESUMO

Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs.


Assuntos
Hiperóxia/fisiopatologia , Respiração , Animais , Animais Recém-Nascidos , Corpo Carotídeo/patologia , Corpo Carotídeo/fisiopatologia , Modelos Animais de Doenças , Feminino , Hiperóxia/patologia , Masculino , Neurônios Aferentes/patologia , Neurônios Aferentes/fisiologia , Pletismografia Total , Ventilação Pulmonar/fisiologia , Ratos Sprague-Dawley , Caracteres Sexuais , Volume de Ventilação Pulmonar/fisiologia
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