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1.
Physiol Rep ; 12(18): e70016, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39294856

RESUMO

The carotid body (CB) senses changes in arterial O2 partial pressure (pO2) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO2 through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)-induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 µmol/mg protein in control rats to 1.45 ± 0.31 µmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione-reducing stress.


Assuntos
Corpo Carotídeo , Diabetes Mellitus Experimental , Glutationa , Mitocôndrias , Ratos Wistar , Animais , Masculino , Corpo Carotídeo/metabolismo , Ratos , Mitocôndrias/metabolismo , Glutationa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Oxirredução
3.
Exp Physiol ; 109(4): 461-469, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38031809

RESUMO

An adequate supply of O2 is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O2 availability or associated with diseases, or a combination of both. Exposure to hypoxia triggers adjustments in multiple physiological systems in the body to generate appropriate homeostatic responses. However, with significant reductions in the arterial partial pressure of O2, hypoxia can be life-threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O2 availability on cellular activity, O2 chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O2, triggering orchestrated responses of increased ventilation and cardiac output, blood flow redistribution and metabolic adjustments. In mammals, the peripheral chemoreceptors of the carotid body are considered to be the main hypoxic sensors and the primary source of excitatory feedback driving respiratory, cardiovascular and autonomic responses. However, current evidence indicates that the CNS contains specialized brainstem and spinal cord regions that can also sense hypoxia and stimulate brain networks independently of the carotid body inputs. In this manuscript, we review the discoveries about the functioning of the O2 chemoreceptors and their contribution to the monitoring of O2 levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O2 homeostasis. We also discuss the implications of the chemoreflex-related mechanisms in paediatric and adult pathologies.


Assuntos
Corpo Carotídeo , Hipóxia , Animais , Humanos , Criança , Células Quimiorreceptoras/fisiologia , Corpo Carotídeo/metabolismo , Respiração , Pulmão , Mamíferos/metabolismo , Oxigênio/metabolismo
4.
Adv Exp Med Biol ; 1427: 99-106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322340

RESUMO

Coronary heart disease (CHD) is a prevalent cardiovascular disease characterized by coronary artery blood flow reductions caused by lipid deposition and oxidation within the coronary arteries. Dyslipidemia is associated with local tissue damage by oxidative stress/inflammation and carotid bodies (CB) peripheral chemoreceptors are heavily modulated by both reactive oxygen species and pro-inflammatory molecules (i.e., cytokines). Despite this, it is not know whether CB-mediated chemoreflex drive may be affected in CHD. In the present study, we evaluated peripheral CB-mediated chemoreflex drive, cardiac autonomic function, and the incidence of breathing disorders in a murine model of CHD. Compared to age-matched control mice, CHD mice showed enhanced CB-chemoreflex drive (twofold increase in the hypoxic ventilatory response), cardiac sympathoexcitation, and irregular breathing disorders. Remarkably, all these were closely linked to the enhanced CB-mediated chemoreflex drive. Our results showed that mice with CHD displayed an enhanced CB chemoreflex, sympathoexcitation, and disordered breathing and suggest that CBs may be involved in chronic cardiorespiratory alterations in the setting of CHD.


Assuntos
Corpo Carotídeo , Insuficiência Cardíaca , Camundongos , Animais , Corpo Carotídeo/fisiologia , Células Quimiorreceptoras/fisiologia , Coração , Sistema Nervoso Autônomo , Hipóxia
5.
Adv Exp Med Biol ; 1427: 107-114, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322341

RESUMO

Heart failure (HF) is a prevalent disease in elderly population. Potentiation of the ventilatory chemoreflex drive plays a pivotal role in disease progression, at least in part, through their contribution to the generation/maintenance of breathing disorders. Peripheral and central chemoreflexes are mainly regulated by carotid body (CB) and the retrotrapezoid nuclei (RTN), respectively. Recent evidence showed an enhanced central chemoreflex drive in rats with nonischemic HF along with breathing disorders. Importantly, increase activity from RTN chemoreceptors contribute to the potentiation of central chemoreflex response to hypercapnia. The precise mechanism driving RTN potentiation in HF is still elusive. Since interdependency of RTN and CB chemoreceptors has been described, we hypothesized that CB afferent activity is required to increase RTN chemosensitivity in the setting of HF. Accordingly, we studied central/peripheral chemoreflex drive and breathing disorders in HF rats with and without functional CBs (CB denervation). We found that CB afferent activity was required to increase central chemoreflex drive in HF. Indeed, CB denervation restored normal central chemoreflex drive and reduced the incidence of apneas by twofold. Our results support the notion that CB afferent activity plays an important role in central chemoreflex potentiation in rats with HF.


Assuntos
Corpo Carotídeo , Insuficiência Cardíaca , Idoso , Ratos , Humanos , Animais , Células Quimiorreceptoras/fisiologia , Corpo Carotídeo/fisiologia , Fenômenos Fisiológicos Respiratórios , Hipercapnia
6.
Adv Exp Med Biol ; 1427: 127-134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322343

RESUMO

Carotid bodies (CBs) are main peripheral chemoreceptors involved in breathing regulation. Despite the well-known role played by CBs on breathing control, the precise contribution of CBs on the regulation of lung mechanics remains controversial. Accordingly, we study changes in lung mechanics in normoxia (FiO2 21%) and hypoxia (FiO2 8%) in mice with or without functional CBs. For this, we used adult male mice that underwent sham or CB denervation (CBD) surgery. Compared to sham-operated mice, we found that CBD induced an increase in lung resistance (RL) while breathing normoxic air (sham vs. CBD, p < 0.05). Importantly, changes in RL were accompanied by an approximately threefold reduction in dynamic compliance (Cdyn). Additionally, end-expiratory work (EEW) was increased in normoxia in the CBD group. Contrarily, we found that CBD has no effect on lung mechanics during hypoxic stimulation. Indeed, RL, Cdyn, and EEW values in CBD mice were undistinguishable from the ones obtained in sham mice. Finally, we found that CBD induces lung parenchyma morphological alterations characterized by reduced alveoli space. Together our results showed that CBD progressively increases lung resistance at normoxic conditions and suggest that CB tonic afferent discharges are needed for the proper regulation of lung mechanics at rest.


Assuntos
Corpo Carotídeo , Masculino , Animais , Camundongos , Corpo Carotídeo/fisiologia , Pulmão , Células Quimiorreceptoras/fisiologia , Hipóxia , Respiração , Denervação
7.
Adv Exp Med Biol ; 1427: 195-201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322350

RESUMO

Ventilatory impairment during aging has been linked to carotid body (CB) dysfunction. Anatomical/morphological studies evidenced CB degeneration and reductions in the number of CB chemoreceptor cells during aging. The mechanism(s) related to CB degeneration in aging remains elusive. Programmed cell death encompasses both apoptosis and necroptosis. Interestingly, necroptosis can be driven by molecular pathways related to low-grade inflammation, one hallmark of the aging process. Accordingly, we hypothesized that necrotic cell death dependent on receptor-interacting protein kinase-3 (RIPK3) may contribute, at least in part, to impair CB function during aging. Adult (3 months) and aged (24 months) wild type (WT) and RIPK3-/- mice were used to study chemoreflex function. Aging results in significant reductions in both the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR). Adult RIPK3-/- mice showed normal HVR and HCVR compared to adult WT mice. Remarkable, aged RIPK3-/- mice displayed no reductions in HVR nor in HCVR. Indeed, chemoreflex responses obtained in aged RIPK3-/- KO mice were undistinguishable from the ones obtained in adult WT mice. Lastly, we found high prevalence of breathing disorders during aging and this was absent in aged RIPK3-/- mice. Together our results support a role for RIPK3-mediated necroptosis in CB dysfunction during aging.


Assuntos
Corpo Carotídeo , Camundongos , Animais , Corpo Carotídeo/fisiologia , Apoptose , Necrose , Células Quimiorreceptoras/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Envelhecimento , Hipercapnia
8.
J Physiol ; 601(24): 5495-5507, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37119020

RESUMO

Obstructive sleep apnoea (OSA), characterized by chronic intermittent hypoxia (CIH), is considered to be an independent risk for hypertension. The pathological cardiorespiratory consequences of OSA have been attributed to systemic oxidative stress, inflammation and sympathetic overflow induced by CIH, but an emerging body of evidence indicates that a nitro-oxidative and pro-inflammatory milieu within the carotid body (CB) is involved in the potentiation of CB chemosensory responses to hypoxia, which contribute to enhance the sympathetic activity. Accordingly, autonomic and cardiovascular alterations induced by CIH are critically dependent on an abnormally heightened CB chemosensory input to the nucleus of tractus solitarius (NTS), where second-order neurons project onto the rostral ventrolateral medulla (RVLM), activating pre-sympathetic neurons that control pre-ganglionic sympathetic neurons. CIH produces oxidative stress and neuroinflammation in the NTS and RVLM, which may contribute to the long-term irreversibility of the CIH-induced alterations. This brief review is mainly focused on the contribution of nitro-oxidative stress and pro-inflammatory molecules on the hyperactivation of the hypoxic chemoreflex pathway including the CB and the brainstem centres, and whether the persistence of autonomic and cardiorespiratory alterations may depend on the glial-related neuroinflammation induced by the enhanced CB chemosensory afferent input.


Assuntos
Corpo Carotídeo , Apneia Obstrutiva do Sono , Humanos , Corpo Carotídeo/fisiologia , Doenças Neuroinflamatórias , Hipóxia , Inflamação/metabolismo , Estresse Oxidativo
9.
Nat Commun ; 14(1): 1725, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977675

RESUMO

Despite advances in the treatment of heart failure, prognosis is poor, mortality high and there remains no cure. Heart failure is associated with reduced cardiac pump function, autonomic dysregulation, systemic inflammation and sleep-disordered breathing; these morbidities are exacerbated by peripheral chemoreceptor dysfunction. We reveal that in heart failure the carotid body generates spontaneous, episodic burst discharges coincident with the onset of disordered breathing in male rats. Purinergic (P2X3) receptors were upregulated two-fold in peripheral chemosensory afferents in heart failure, and when antagonized abolished these episodic discharges, normalized both peripheral chemoreceptor sensitivity and the breathing pattern, reinstated autonomic balance, improved cardiac function, and reduced both inflammation and biomarkers of cardiac failure. Aberrant ATP transmission in the carotid body triggers episodic discharges that via P2X3 receptors play a crucial role in the progression of heart failure and as such offer a distinct therapeutic angle to reverse multiple components of its pathogenesis.


Assuntos
Corpo Carotídeo , Insuficiência Cardíaca , Ratos , Masculino , Animais , Receptores Purinérgicos P2X3 , Células Quimiorreceptoras/fisiologia , Respiração
10.
Medicine (Baltimore) ; 102(1): e32295, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607871

RESUMO

Adjunctive therapy for hypertension is in high demand for clinical research. Therefore, several meta-analyses have provided sufficient evidence for meditation as an adjunct therapy, without being anchored on reliable physiological grounds. Meditation modulates the autonomic nervous system. Herein, we propose a hierarchical-dependent effect for the carotid body (CB) in attenuating blood pressure (BP) and ventilatory variability (VV) fine-tuning due to known nerve connections between the CB, prefrontal brain, hypothalamus, and solitary tract nucleus. The aim of this exploratory study was to investigate the role of CB in the possible decrease in BP and changes in VV that could occur in response to meditation. This was a prospective, single-center, parallel-group, randomized, controlled clinical trial with concealed allocation. Eligible adult subjects of both sexes with stage 1 hypertension will be randomized into 1 of 2 groups: transcendental meditation or a control group. Subjects will be invited to 3 visits after randomization and 2 additional visits after completing 8 weeks of meditation or waiting-list control. Thus, subjects will undergo BP measurements in normoxia and hyperoxia, VV measurements using the Poincaré method at rest and during exercise, and CB activity measurement in the laboratory. The primary outcome of this study was the detection of changes in BP and CB activity after 8 weeks. Our secondary outcome was the detection of changes in the VV at rest and during exercise. We predict that interactions between hyperoxic deactivation of CB and meditation; Will reduce BP beyond stand-alone intervention or alternatively; Meditation will significantly attenuate the effects of hyperoxia as a stand-alone intervention. In addition, VV can be changed, partially mediated by a reduction in CB activity. Trial registration number: ReBEC registry (RBR-55n74zm). Stage: pre-results.


Assuntos
Corpo Carotídeo , Hiperóxia , Hipertensão , Meditação , Adulto , Masculino , Feminino , Humanos , Meditação/métodos , Estudos Prospectivos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Front Immunol ; 13: 1033774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389846

RESUMO

The idea that the nervous system communicates with the immune system to regulate physiological and pathological processes is not new. However, there is still much to learn about how these interactions occur under different conditions. The carotid body (CB) is a sensory organ located in the neck, classically known as the primary sensor of the oxygen (O2) levels in the organism of mammals. When the partial pressure of O2 in the arterial blood falls, the CB alerts the brain which coordinates cardiorespiratory responses to ensure adequate O2 supply to all tissues and organs in the body. A growing body of evidence, however, has demonstrated that the CB is much more than an O2 sensor. Actually, the CB is a multimodal sensor with the extraordinary ability to detect a wide diversity of circulating molecules in the arterial blood, including inflammatory mediators. In this review, we introduce the literature supporting the role of the CB as a critical component of neuroimmune interactions. Based on ours and other studies, we propose a novel neuroimmune pathway in which the CB acts as a sensor of circulating inflammatory mediators and, in conditions of systemic inflammation, recruits a sympathetic-mediated counteracting mechanism that appears to be a protective response.


Assuntos
Corpo Carotídeo , Animais , Neuroimunomodulação , Oxigênio/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Mamíferos/metabolismo
13.
Medicina (Kaunas) ; 58(4)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35454388

RESUMO

Background and Objectives: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin Ob-Rb and of c-Fos mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. Materials and Methods: The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO2, pCO2, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; n = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS (n = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS (n = 10); (d) control 2, aCSF in cNTS and saline in the ICS (n = 10). Results: Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin Ob-Rb mRNA receptor expression, with no significant increases in c-Fos mRNA in the NTSc. Conclusions: Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in Ob-Rb receptors, without persistent changes in neuronal activation.


Assuntos
Corpo Carotídeo , Leptina , Receptores para Leptina , Núcleo Solitário , Animais , Glicemia/metabolismo , Corpo Carotídeo/metabolismo , Glucose/metabolismo , Hipóxia , Leptina/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/metabolismo , Núcleo Solitário/metabolismo
14.
Physiology (Bethesda) ; 37(3): 128-140, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34866399

RESUMO

Emergent evidence indicates that the carotid body (CB) chemoreceptor may sense systemic inflammatory molecules and is an afferent arm of the anti-inflammatory reflex. Moreover, a proinflammatory milieu within the CB is involved in the enhanced CB chemosensory responsiveness to oxygen following sustained and intermittent hypoxia. In this review, we focus on the physiopathological participation of CBs in inflammatory diseases, such as sepsis and intermittent hypoxia.


Assuntos
Corpo Carotídeo , Anti-Inflamatórios/uso terapêutico , Humanos , Hipóxia/patologia , Inflamação/patologia , Reflexo
15.
Sci Rep ; 11(1): 14458, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262072

RESUMO

Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6 week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF + EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF + EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF + EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (~ 60% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF + EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.


Assuntos
Corpo Carotídeo , Insuficiência Cardíaca , Animais , Arritmias Cardíacas , Hipercapnia , Hipóxia , Ratos , Reflexo
16.
Rev. colomb. cir ; 36(2): 257-267, 20210000. fig
Artigo em Espanhol | LILACS | ID: biblio-1223912

RESUMO

Introducción. El carcinoma del glomus carotideo es infrecuente y se presenta en el 6 % de los paragangliomas carotideos. Suele haber dificultad en su diagnóstico preoperatorio y no se diferencia fácilmente de su contraparte benigna, lo que puede conllevar a complicaciones quirúrgicas. Este trabajo describe la experiencia en su abordaje clínico y quirúrgico en una serie de casos, además de una revisión de la literatura profundizando en su diagnóstico, abordaje terapéutico, sobrevida y mortalidad. Métodos. De los pacientes operados por glomus carotideos durante un periodo de 20 años, se identificaron aquellos llevados a cirugía por carcinoma. Se realizó una búsqueda bibliográfica extensa en PubMed, haciendo énfasis en diagnóstico y tratamiento. Resultados. De un total de 139 pacientes sometidos a cirugía de resección de tumor del cuerpo carotideo, tres pacientes (2,2 %) presentaron carcinoma. Dos tenían metástasis cervicales y uno metástasis hepáticas. Uno presentaba glomus bilateral asociado a trastorno genético de origen familiar. Se realizó cirugía y adyuvancia en todos los casos. Discusión. El diagnóstico diferencial preoperatorio entre glomus benigno y maligno es difícil, por lo cual deben buscarse hallazgos clínicos o factores de riesgo que puedan sugerir malignidad. Las imágenes pocas veces muestran características claras de invasión vascular. Siempre que sea posible, en el tratamiento del cáncer del glomus carotideo, debe realizarse resección quirúrgica, acompañada de un vaciamiento funcional de cuello, dejando la radioterapia, la quimioterapia y la hormonoterapia como terapias adyuvantes


Introduction. Carcinoma of the carotid glomus is rare and occurs in 6% of carotid paragangliomas. There is often difficulty in its preoperative diagnosis, and it is not easily differentiated from its benign counterpart, which can lead to surgical complications. This study describes the experience in its clinical and surgical approach in a series of cases, as well as a review of the literature of its diagnosis, therapeutic approach, survival, and mortality.Methods. Of the patients operated for carotid glomus over a 20-year period, those undergoing surgery for carcinoma were identified. An extensive literature search was conducted in PubMed, with an emphasis on diagnosis and treatment.Results. Out of a total of 139 patients who underwent carotid body tumor resection surgery, three patients (2.2%) had carcinoma. Two had cervical metastases and one had liver metastases. One had bilateral glomus associated with a genetic disorder of familial origin. Surgery and adjuvant surgery were performed in all cases.Discussion. The preoperative differential diagnosis between benign and malignant glomus is difficult, for which clinical findings or risk factors that may suggest malignancy should be sought. Images rarely show clear features of vascular invasion. Whenever possible in the treatment of carotid glomus cancer, surgical resection should be performed, accompanied by a functional neck dissection, leaving radiotherapy, chemotherapy, and hormone therapy as adjuvant therapies


Assuntos
Humanos , Corpo Carotídeo , Paraganglioma , Neoplasias
17.
Physiol Rev ; 101(3): 1177-1235, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33570461

RESUMO

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 and pH, eliciting reflex ventilatory, cardiovascular, and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiological responses, and its role in maintaining health and potentiating disease. Emphasis is placed on 1) transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ion channels; 2) synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; 3) integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological, or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and 4) the contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension, and metabolic diseases and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.


Assuntos
Sistema Nervoso Autônomo/metabolismo , Corpo Carotídeo/metabolismo , Células Quimiorreceptoras/metabolismo , Hipóxia/metabolismo , Animais , Sistema Cardiovascular/metabolismo , Humanos
18.
Respir Physiol Neurobiol ; 285: 103593, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33276092

RESUMO

The carotid body's glomus cells are the primary sensors of hypoxia in mammals. Previous studies suggested that the glomus cells' hypoxia sensitivity is mediated by lactate in mice. This molecule increases the intracellular [Ca2+] and induces exocytosis in glomus cells, activating the carotid sinus nerve (the axons of chemoreceptive petrosal neurons). On the other hand, how lactate affects the activity of carotid body of rats is still unknown. We hypothesized that lactate activates the carotid body of rats. In Wistar rats, we measured the changes in the electrical properties of isolated glomus cells and petrosal chemoreceptive neurons in in situ preparations in response to different concentrations of lactate. Superfusion of both physiological and supraphysiological concentrations of lactate did not affect the membrane conductance and potential of glomus cells. Moreover, lactate injected into the carotid body did not activate the anatomically and physiologically identified chemoreceptive petrosal neurons. We conclude that the carotid body of Wistar rats is not sensitive to lactate.


Assuntos
Corpo Carotídeo/metabolismo , Células Quimiorreceptoras/fisiologia , Ácido Láctico/metabolismo , Potenciais da Membrana/fisiologia , Animais , Corpo Carotídeo/efeitos dos fármacos , Células Quimiorreceptoras/efeitos dos fármacos , Ácido Láctico/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Wistar
19.
Cuad. Hosp. Clín ; 61(2): 23-32, dic. 2020. ilus.
Artigo em Espanhol | LILACS, LIBOCS | ID: biblio-1179084

RESUMO

OBJETIVO: proponer una clasificación preoperatoria a los pacientes con tumor de cuerpo Carotídeo y relacionarlos con complicaciones postoperatorias. MATERIAL Y MÉTODOS: todos los pacientes operados con diagnóstico de tumor del cuerpo Carotídeo entre el 2005 al 2014 en el Hospital Obrero N° 1 de la Caja Nacional de Salud en La Paz - Bolivia RESULTADOS: se analizaron y operaron 115 pacientes con un promedio de edad de 52 años (DE±11,725 y una moda de 57 años) de los cuales el 109 (94,80%) correspondieron al género femenino con una razón de 18:1. Todos los pacientes eran originarios y residentes de ciudades ubicadas a más de 2500 m.s.n.m. El promedio de evolución fue de 3 años (DE±2,189), y solo 7 pacientes (6,1%) presentan hábito tabáquico. 83 pacientes (72,2%) de los TCC se localizan en el lado izquierdo En las manifestaciones clínicas, todos los pacientes presentan el tumor localizado en el ángulo mandibular, por delante del musculo esternocleidomastoideo, describiéndose un crecimiento paulatino y permanente en 72 sujetos (62,6%), cefalea en 45 (39,1%), presencia de latido en 30 sujetos (26,1%), disfagia en 9 (7,9%), mareos en 16 (13,9%) y disfonía en 6 (5,2%). Entre los signos más evidentes de TCC, se describe el signo de Fontaine en 114 sujetos (99,2%), adenomegalia en 20 (17,4%) y otros menos frecuentes como soplo, abombamiento parafaringeo y compromiso de pares craneales. Todos los pacientes fueron clasificados en ambos sistemas (Shamblin y la nuestra llamada de los Andes). Se describen 39 pacientes (33,2%) con complicaciones postoperatorias, Grado I: 1 paciente sin complicaciones; Grado II: de 58 sujetos, 4 (3,5%) presentaban parálisis temporal del Hipogloso; en el Grado III: de los 41 sujetos, 24 (20,8%) presentaron ligadura de la arteria carótida externa, parálisis del hipogloso y glosofaringeo, lesión de recurrente y del laríngeo superior. En el grupo IV, de los 15 sujetos operados, 11 presentaron complicaciones (9,6% del total y 73% del grupo) entre las cuales están ligadura de la arteria carótida externa, lesión del hipogloso y un paciente con AVC y hemiparesia. Se describe una reoperación (0,86%) y ninguna mortalidad. CONCLUSIÓN: proponer una clasificación preoperatoria que tenga la posibilidad de asociarse a complicaciones y pronóstico.


OBJECTIVE: to propose a preoperative classification of patients with Carotid Body Tumor and relate them to postoperative complications. MATERIAL AND METHODS: all patients operated with a diagnosis of Carotid Body Tumor between 2005 and 2014 at the Obrero Hospital No. 1 of the National Health Fund in La Paz - Bolivia RESULTS: 115 patients with an average age of 52 years (SD±11.725 and a mode of 57 years) were analyzed and operated on, of which 109 (94.80%) corresponded to the female gender with a ratio of 18: 1. All the patients were from and residents of cities located more than 2,500 meters above sea level. The mean evolution was 3 years (SD±2.189), and only 7 patients (6.1%) had a smoking habit. 83 patients (72.2%) of CBTs are located on the left side In the clinical manifestations, all patients present the tumor located in the mandibular angle, in front of the sternocleidomastoid muscle, describing a gradual and permanent growth in 72 subjects (62.6%), headache in 45 (39.1%), presence of heartbeat in 30 subjects (26.1%), dysphagia in 9 (7.9%), dizziness in 16 (13.9%) and dysphonia in 6 (5.2%). Among the most obvious signs of CBT, the Fontaine sign is described in 114 subjects (99.2%), adenomegaly in 20 (17.4%) and other less frequent signs such as murmur, parapharyngeal bulging and cranial nerve involvement. All patients were classified in both systems (Shamblin and ours called from the Andes). 39 patients (33.2%) with postoperative complications were described, grade I: 1 patient without complications; Grade II: of 58 subjects, 4 (3.5%) had temporary hypoglossal paralysis; in Grade III: of the 41 subjects, 24 (20.8%) presented external carotid artery ligation, hypoglossal and glossopharyngeal paralysis, recurrent lesion and superior larynx. In group IV, of the 15 operated subjects, 11 presented complications (9.6% of the total and 73% of the group), among which are external carotid artery ligation, hypoglossal injury and one patient with stroke and hemiparesis. A reoperation (0.86%) and no mortality are described. CONCLUSION: propose a preoperative classification that has the possibility of being associated with complications and prognosis.


Assuntos
Humanos , Corpo Carotídeo , Tumor do Corpo Carotídeo , Cefaleia , Sinais e Sintomas , Neoplasias
20.
J Endocrinol ; 247(1): 101-114, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32755993

RESUMO

Many diseases of the respiratory system occur differently in males and females, indicating a possible role of gonadal hormones in respiratory control. We hypothesized that testosterone (T) is important for the ventilatory chemosensitivity responses in males. To test this hypothesis, we evaluated ventilation (V̇ E), metabolic rate and body temperature (Tb) under normoxia/normocapnia, hypercapnia and hypoxia in orchiectomized (ORX), ORX with testosterone replacement (ORX + T) or flutamide (FL, androgen receptor blocker)-treated rats. We also performed immunohistochemistry to evaluate the presence of androgen receptor (AR) in the carotid body (CB) of intact males. Orchiectomy promoted a reduction V̇ E and ventilatory equivalent (V̇ E /V̇ O2) under room-air conditions, which was restored with testosterone treatment. Moreover, during hypoxia or hypercapnia, animals that received testosterone replacement had a higher V̇ E and V̇ E /V̇ O2 than control and ORX, without changes in metabolic and thermal variables. Flutamide decreased the hypoxic ventilatory response without changing the CO2-drive to breathe, suggesting that the testosterone effect on hypercapnic hyperventilation does not appear to involve the AR. We also determined the presence of AR in the CB of intact animals. Our findings demonstrate that testosterone seems to be important for maintaining resting V̇ E in males. In addition, the influence of testosterone on V̇ E, either during resting conditions or under hypoxia and hypercapnia, seems to be a direct and specific effect, as no changes in metabolic rate or Tb were observed during any treatment. Finally, a putative site of testosterone action during hypoxia is the CB, since we detected the presence of AR in this structure.


Assuntos
Regulação da Temperatura Corporal/fisiologia , Hipercapnia/fisiopatologia , Hipóxia/fisiopatologia , Fenômenos Fisiológicos Respiratórios , Testosterona/fisiologia , Antagonistas de Receptores de Andrógenos/farmacocinética , Animais , Corpo Carotídeo/química , Flutamida/farmacologia , Masculino , Orquiectomia , Consumo de Oxigênio/fisiologia , Ratos , Ratos Wistar , Receptores Androgênicos/análise , Receptores Androgênicos/fisiologia , Testosterona/administração & dosagem
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