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Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia

Abstract

The neural mechanisms underlying the generation and modulation of the sympathetic outflow and the respiratory motor activities are essential for the physiological regulation of the cardiovascular and respiratory functions and consequently for the maintenance of the life. Changes in any aspect of these complex neural mechanisms may affect the cardiovascular and respiratory functions and generating pathophysiological conditions such as hypertension and obstructive sleep apnea. Taking into account that the groups of neurons underlying both sympathetic and respiratory activities are located in the ventral aspect of the medulla, and also that we have strong experimental evidences of the coupling of these activities, the main purpose of this Program Project Grant (Thematic Project) is to evaluate the neurochemical mechanisms involved in the sympathetic-respiratory coupling, especially under challenges conditions such as the chronic intermittent hypoxia or sustained hypoxia. To reach this goal, we will use several contemporary methods and procedures appropriated to help us to answer the several fundamental questions of this Project. In order to challenge the neural pathways of the peripheral chemo reflex and consequently to induce changes in the sympathetic respiratory coupling, we will use different experimental protocols of hypoxia (intermittent or sustained). To explore the complexity of the neural network involved in the generation of sympathetic and respiratory activities we will use several methods of advanced electrophysiology and cellular biology, which we were able to introduce successfully in our laboratory on the past few years, with the financial support by6FAPESP. On the 11 sub-projects to be developed, we will use from awake freely moving rats to neurons in the slices of the brainstem to evaluated very precise ionic currents that may determine the electrophysiological profile of each group of sympathetic and respiratory neurons in normal and in rats submitted to hypoxia. With this integrated approach from whole animal to isolated neurons, not usual in the large majority of laboratories in the world, we are convinced that the obtained results will contribute very much for a better understanding of the neural mechanisms underlying different pathophysiological conditions such as the neurogenic hypertension. (AU)

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Scientific publications (26)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ACCORSI-MENDONCA, DANIELA; DA SILVA, MELINA P.; SOUZA, GEORGE M. P. R.; LIMA-SILVEIRA, LUDMILA; KARLEN-AMARANTE, MARLUSA; AMORIM, MATEUS R.; ALMADO, CARLOS E. L.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Pacemaking Property of RVLM Presympathetic Neurons. FRONTIERS IN PHYSIOLOGY, v. 7, . (13/06077-5)
MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; ANTUNES-RODRIGUES, JOSE; MACHADO, BENEDITO H.. Respiratory Network Enhances the Sympathoinhibitory Component of Baroreflex of Rats Submitted to Chronic Intermittent Hypoxia. Hypertension, v. 68, n. 4, p. 1021-1030, . (13/06077-5, 13/10484-5)
MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Electrophysiological properties of laryngeal motoneurones in rats submitted to chronic intermittent hypoxia. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 3, p. 619-634, . (13/06077-5, 13/10484-5)
ACCORSI-MENDONCA, DANIELA; ALMADO, CARLOS E. L.; BONAGAMBA, LENI G. H.; CASTANIA, JACI A.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Enhanced Firing in NTS Induced by Short-Term Sustained Hypoxia Is Modulated by Glia-Neuron Interaction. JOURNAL OF NEUROSCIENCE, v. 35, n. 17, p. 6903-6917, . (13/06077-5)
BITTENCOURT-SILVA, PALOMA G.; MENEZES, MIGUEL FURTADO; MENDONCA-JUNIOR, BOLIVAL A.; KARLEN-AMARANTE, MARLUSA; ZOCCAL, DANIEL B.. Postnatal intermittent hypoxia enhances phrenic and reduces vagal upper airway motor activities in rats by epigenetic mechanisms. Experimental Physiology, v. 105, n. 1, p. 148-159, . (13/06077-5, 13/17251-6)
DA SILVA, MELINA P.; MORAES, DAVI JOSE A.; BONAGAMBA, LENI G. H.; MECAWI, ANDRE DE SOUZA; VARANDA, WAMBERTO A.; MACHADO, BENEDITO H.. Hyperexcitability and plasticity induced by sustained hypoxia on rectus abdominis motoneurons. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1935-1956, . (13/06077-5, 13/10484-5)
SOUZA, GEORGE M. P. R.; BARNETT, WILLIAM H.; AMORIM, MATEUS R.; LIMA-SILVEIRA, LUDMILA; MORAES, DAVI J. A.; MOLKOV, I, YAROSLAV; MACHADO, BENEDITO H.. Pre- and post-inspiratory neurons change their firing properties in female rats exposed to chronic intermittent hypoxia. Neuroscience, v. 406, p. 467-486, . (13/06077-5, 15/06550-8)
MORAES, DAVI J. A.; DA SILVA, MELINA P.; SPILLER, PEDRO F.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Purinergic plasticity within petrosal neurons in hypertension. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 315, n. 5, p. R963-R971, . (15/01073-7, 13/06077-5, 16/24869-4, 13/10484-5)
SOUZA, GEORGE MIGUEL P. R.; AMORIM, MATEUS R.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Sex differences in the respiratory-sympathetic coupling in rats exposed to chronic intermittent hypoxia. Respiratory Physiology & Neurobiology, v. 256, n. SI, p. 109-118, . (13/06077-5, 15/06550-8)
MENEZES, MIGUEL F.; ZOCCAL, DANIEL. CARDIORESPIRATORY CONTROL IN NEWBORN RATS SUBMITTED TO CHRONIC INTERMITTENT HYPOXIA. FASEB JOURNAL, v. 30, p. 1-pg., . (13/06077-5)
ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; FLOR, KARINE C.; DA SILVA, MELINA P.; COSTA-SILVA, JOAO H.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; MURPHY, DAVID; PATON, JULIAN F. R.. Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats. Experimental Physiology, v. 104, n. 9, p. 1371-1383, . (13/06077-5, 15/23467-7, 13/10484-5)
SOUZA, GEORGE MIGUEL P. R.; AMORIM, MATEUS R.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Sex differences in the respiratory-sympathetic coupling in rats exposed to chronic intermittent hypoxia. Respiratory Physiology & Neurobiology, v. 256, p. 10-pg., . (15/06550-8, 13/06077-5)
MORAES, DAVI J. A.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 14, p. 3055-3063, . (13/06077-5, 13/10484-5)
PERIM, RAPHAEL R.; AMORIM, MATEUS R.; BONAGAMBA, THE LATE LENI G. H.; MACHADO, BENEDITO H.. Previous exposure to chronic intermittent hypoxia blunts the development of one-kidney, one-clip hypertension in rats. Experimental Physiology, v. 103, n. 4, p. 473-482, . (13/06077-5)
ACCORSI-MENDONCA, DANIELA; BONAGAMBA, LENI G. H.; MACHADO, BENEDITO H.. Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia. Journal of Neurophysiology, v. 121, n. 5, p. 1822-1830, . (13/06077-5)
LIMA-SILVEIRA, LUDMILA; ACCORSI-MENDONCA, DANIELA; BONAGAMBA, LENI G. H.; ALMADO, CARLOS EDUARDO L.; DA SILVA, MELINA P.; NEDOBOY, POLINA E.; PILOWSKY, PAUL M.; MACHADO, BENEDITO H.. Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 11, p. 2903-2923, . (13/06077-5, 14/11101-5, 17/13720-2)
MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.. Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats. SCIENTIFIC REPORTS, v. 7, . (13/06077-5, 15/01073-7, 13/10484-5)
AMORIM, MATEUS R.; PENA, RODRIGO F. O.; SOUZA, GEORGE M. P. R.; BONAGAMBA, LENI G. H.; ROQUE, ANTONIO C.; MACHADO, BENEDITO H.. Firing properties of ventral medullary respiratory neurons in sino-aortic denervated rats. Experimental Physiology, v. 104, n. 1, p. 39-49, . (13/06077-5, 15/50122-0, 13/15195-1, 13/07699-0, 13/25667-8)
AMORIM, MATEUS R.; BONAGAMBA, LENI G. H.; SOUZA, GEORGE M. P. R.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino-aortic denervated rats. Experimental Physiology, v. 102, n. 9, p. 1100-1117, . (13/06077-5, 13/15195-1)
BAZILIO, DARLAN S.; BONAGAMBA, LENI G. H.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Cardiovascular and respiratory profiles during the sleep-wake cycle of rats previously submitted to chronic intermittent hypoxia. Experimental Physiology, v. 104, n. 9, p. 1408-1419, . (13/06077-5)
AMORIM, MATEUS R.; SOUZA, GEORGE MIGUEL P. R.; MACHADO, BENEDITO H.. Possible Breathing Influences on the Control of Arterial Pressure After Sino-aortic Denervation in Rats. CURRENT HYPERTENSION REPORTS, v. 20, n. 1, . (13/06077-5, 13/15195-1)
MAGALHAES, KAROLYNE S.; SPILLER, PEDRO F.; DA SILVA, MELINA P.; KUNTZE, LUCIANA B.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats. SCIENTIFIC REPORTS, v. 8, . (13/10484-5, 15/01073-7, 17/09071-9, 16/24869-4, 13/06077-5)
PIJACKA, WIOLETTA; MORAES, DAVI J. A.; RATCLIFFE, LAURA E. K.; NIGHTINGALE, ANGUS K.; HART, EMMA C.; DA SILVA, MELINA P.; MACHADO, BENEDITO H.; MCBRYDE, FIONA D.; ABDALA, ANA P.; FORD, ANTHONY P.; et al. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature Medicine, v. 22, n. 10, p. 1151-1159, . (13/06077-5, 13/10484-5)
TAXINI, CAMILA L.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.; ZOCCAL, DANIEL B.. ROLE OF A5 NORADRENERGIC NEURONS IN THE CHEMOREFLEX CONTROL OF RESPIRATORY AND SYMPATHETIC ACTIVITIES IN UNANESTHETIZED CONDITIONS. Neuroscience, v. 354, p. 146-157, . (13/06077-5, 13/17251-6)
ZOCCAL, DANIEL B.. Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho-excitation. Experimental Physiology, v. 100, n. 2, p. 143-148, . (09/54888-7, 13/06077-5)
DRAGER, LUCIANO F.; POLOTSKY, VSEVOLOD Y.; O'DONNELL, CHRISTOPHER P.; CRAVO, SERGIO L.; LORENZI-FILHO, GERALDO; MACHADO, BENEDITO H.. Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 7, p. H1101-H1111, . (12/02953-2, 13/06077-5)

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