RESUMEN
KEY POINTS: Carotid body (CB) chemoreceptors are hyperactive in hypertension, and their acute activation produces bronchoconstriction. We show that the respiratory-modulated bronchiolar tone, pulmonary parasympathetic efferent activity, and the firing frequency and synaptic excitation of bronchoconstrictor motoneurones in the nucleus ambiguus were all enhanced in spontaneous hypertensive (SH) rats. In SH rats, CB denervation reduced the respiratory-related parasympathetic-mediated bronchoconstrictor tone to levels seen in normotensive rats. Chemoreflex evoked bronchoconstrictor tone was heightened in SH versus normotensive rats. The intrinsic electrophysiological properties and morphology of bronchoconstrictor motoneurones were similar across rat strains. The heightened respiratory modulation of parasympathetic-mediated bronchoconstrictor tone to the airways in SH rats is caused by afferent drive from the CBs. ABSTRACT: Much research has described heightened sympathetic activity in hypertension and diminished parasympathetic tone, especially to the heart. The carotid body (CB) chemoreceptors exhibit hyperreflexia and are hyperactive, providing excitatory drive to sympathetic networks in hypertension. Given that acute CB activation produces reflex evoked bronchoconstriction via activation of parasympathetic vagal efferents, we hypothesised that the parasympathetic bronchoconstrictor activity is enhanced in spontaneously hypertensive (SH) rats and that this is dependent on CB inputs. In situ preparations of Wistar and SH rats were used in which bronchiolar tone, the pulmonary branch of the vagus (pVN) and phrenic nerves were recorded simultaneously; whole cell patch clamp recordings of bronchoconstrictor vagal motoneurones were also made from the nucleus ambiguus. Bronchiolar tone, pVN and bronchoconstrictor motoneurones were respiratory modulated and this modulation was enhanced in SH rats. These differences were all eliminated after CB denervation. Stimulation of the CBs increased the phrenic frequency that caused a summation of the respiratory-related increases in pVN, resulting in the development of bronchoconstrictor tone. This tone was exaggerated in SH rats. The enhanced respiratory-parasympathetic coupling to airways in SH rats was not due to differences in the intrinsic electrophysiological properties of bronchoconstrictor motoneurones but reflected heightened pre-inspiratory- and inspiratory-related synaptic drive. In summary, in SH rats the phasic respiratory modulation of parasympathetic tone to the airways is elevated and the greater development of this bronchoconstrictor tone is caused by the heightened afferent drive originating from the CBs. Thus, targeting the CBs may prove effective for increasing lower airway patency.
Asunto(s)
Hipertensión , Animales , Presión Sanguínea , Bulbo Raquídeo , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
NEW FINDINGS: What is the central question of this study? What is the carotid bodies' contribution to active inspiratory and expiratory response to exercise? What is the main finding and its importance? Removal of the carotid bodies reduced the active inspiratory and expiratory responses of diaphragm and abdominal internal oblique muscles, respectively, to high-intensity, but not to low-intensity, exercise in rats. Removal of the carotid bodies increased PaCO2 and decreased arterial pH in response to high-intensity exercise. The carotid bodies contribute to the inspiratory and expiratory adjustments to high-intensity exercise in rats. ABSTRACT: Exercise involves the interaction of several physiological processes, in which adjustments in pulmonary ventilation occur in response to increased O2 consumption, CO2 production and altered acid-base equilibrium. The peripheral chemoreceptors (carotid bodies; CBs) are sensitive to changes in the chemical composition of arterial blood, and their activation induces active inspiratory and expiratory responses. Herein, we tested the hypothesis that the CBs contribute to the active inspiratory and expiratory responses to exercise in rats. We performed electromyographic recordings of the diaphragm (DiaEMG ) and abdominal internal oblique (AbdEMG ) muscles in rats before and after bilateral removal of the CBs (CBX) during constant-load low-intensity and high-intensity progressive treadmill exercise. We also collected arterial blood samples for gaseous and pH analyses. Similar increases in DiaEMG frequency in both experimental conditions (before and after CBX) during low-intensity exercise were observed, without significant changes in the DiaEMG amplitude. During high-intensity exercise, lower responses of both DiaEMG frequency and DiaEMG amplitude were observed in rats after CBX. The AbdEMG phasic active expiratory response was not significant either before or after CBX during low-intensity exercise. However, CBX reduced the phasic active expiratory responses during high-intensity exercise. The blunted responses of inspiratory and expiratory adjustments to high-intensity exercise after CBX were associated with higher PaCO2 levels and lower arterial pH values. Our data show that in rats the CBs do not participate in the inspiratory and expiratory responses to low-intensity exercise, but are involved in the respiratory compensation against the metabolic acidosis induced by high-intensity exercise.
Asunto(s)
Cuerpo Carotídeo/fisiología , Espiración/fisiología , Inhalación/fisiología , Condicionamiento Físico Animal/fisiología , Animales , Diafragma/fisiología , Electrodos Implantados , Electromiografía , Ventilación Pulmonar , Ratas , Ratas WistarRESUMEN
Os paragangliomas são neoplasias de células neuroendócrinas (Paraneurônios) do sistema parassimpático (Paraganglia), e ocorrem normalmente no corpo aórtico (base do coração) e carotídeo (pescoço). São tumores raros, frequentemente benignos, que podem raramente metastatizar. Raças braquiocefálicas e animais que vivem em elevadas altitudes são mais predispostos ao desenvolvimento de paragangliomas. Esta revisão bibliográfica objetiva-se descrever as manifestações clínicas, etiopatogenia, formas de diagnóstico e tratamento dos paragangliomas.
The paraganglioms are neoplasms of neuroendocrine cells (Paraneurons) of the parasympathetic system (Paraganglia). Normally occur on the aortic (base of heart) and carotid (neck) bodies. They are rare tumors, frequently beginners and its rarely able to metastasize. Braquicephalics breeds and animals that live in high altitudes are more predisposed to developing paraganglioms. This bibliographic review describes clinical manifestation, etiopathogeny and types of diagnosis and treatment of the paraganglioms.
Los paragangliomas son neoplasias de las células neuroendocrinas (Paraneuronas) del sistema parasimpático (Paraganglios) y ocurren normalmente en el cuerpo aórtico (base del corazón) y carótida (cuello). Son tumores raros, frecuentemente benignos, que pueden raramente ocurrir metástasis. Razas braquiocefálicas y animales que viven en altas altitudes son más predispuestos al desenvolvimiento de paragangliomas. Esta revisión bibliográfica describe las manifestaciones clínicas, etiopatogenia, método de diagnóstico y tratamiento de los paragangliomas.
Asunto(s)
Paraganglioma/cirugía , Paraganglioma/diagnóstico , Paraganglioma/epidemiología , Paraganglioma/etiología , Paraganglioma/fisiopatología , Paraganglioma/terapia , Paraganglioma/veterinariaRESUMEN
Os paragangliomas são neoplasias de células neuroendócrinas (Paraneurônios) do sistema parassimpático (Paraganglia), e ocorrem normalmente no corpo aórtico (base do coração) e carotídeo (pescoço). São tumores raros, frequentemente benignos, que podem raramente metastatizar. Raças braquiocefálicas e animais que vivem em elevadas altitudes são mais predispostos ao desenvolvimento de paragangliomas. Esta revisão bibliográfica objetiva-se descrever as manifestações clínicas, etiopatogenia, formas de diagnóstico e tratamento dos paragangliomas.(AU)
The paraganglioms are neoplasms of neuroendocrine cells (Paraneurons) of the parasympathetic system (Paraganglia). Normally occur on the aortic (base of heart) and carotid (neck) bodies. They are rare tumors, frequently beginners and its rarely able to metastasize. Braquicephalics breeds and animals that live in high altitudes are more predisposed to developing paraganglioms. This bibliographic review describes clinical manifestation, etiopathogeny and types of diagnosis and treatment of the paraganglioms.(AU)
Los paragangliomas son neoplasias de las células neuroendocrinas (Paraneuronas) del sistema parasimpático (Paraganglios) y ocurren normalmente en el cuerpo aórtico (base del corazón) y carótida (cuello). Son tumores raros, frecuentemente benignos, que pueden raramente ocurrir metástasis. Razas braquiocefálicas y animales que viven en altas altitudes son más predispuestos al desenvolvimiento de paragangliomas. Esta revisión bibliográfica describe las manifestaciones clínicas, etiopatogenia, método de diagnóstico y tratamiento de los paragangliomas.(AU)