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Involvement of serotoninergic mechanisms of the retrotrapezoid nucleus in the sympathetic and respiratory changes induced by intermitente hypoxia

Grant number: 14/06976-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Physiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Daniel Breseghello Zoccal
Grantee:Eduardo Vieira Lemes
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:09/54888-7 - Neural mechanisms involved on chemoreception, AP.TEM

Abstract

In conditions of hypoxia (low partial pressure of O2) or hypercapnia (high partial pressure of CO2), reflex mechanisms are activated to trigger cardiovascular (increased sympathetic activity and blood pressure) and respiratory responses (increased alveolar ventilation) to restore blood gas homeostasis. These cardiorespiratory responses are initiated by the activation of chemosensitive cells strategically located in the carotid bodies (peripheral chemoreceptors, mainly responsive to changes in arterial blood O2) and in the brainstem (central chemoreceptors, sensitive to changes in arterial blood CO2/pH), which send excitatory drive to respiratory and sympathetic neurons. Although separate anatomically, experimental evidence indicates that peripheral chemoreceptors can interact with the central chemoreceptors, exerting an additive effect on the responses induced by hypercapnia. Such interaction has pathological relevance, since changes in the mechanisms monitoring arterial O2 and CO2 levels contribute to increased sympathetic basal activity and the development of hypertension. Experimental evidence shows that animals subjected to intermittent hypoxia (IH) have elevated basal sympathetic activity associated with marked changes in breathing pattern, with the generation active expiratory pattern. Studies involving mathematical models suggest the involvement of retrotrapezoid nucleus (RTN) - important nucleus involved in central chemoreception - the HI-induced sympathetic and respiratory changes. However, there is no functional evidence elucidating the role of RTN neurons and the potential neurochemical mechanisms responsible for the activation of these neurons after IH exposure. Accordingly, in this project we considered the original hypothesis that the sympathetic and respiratory changes observed in rats submitted to IH result from increased sensitivity/excitability of RTN chemosensitive neurons as a consequence of the activation of serotonergic mechanisms. To explore this possibility, we will use the technique of decerebrated arterially-perfused in situ rat preparations, which will be exposed to HI in association with the simultaneous recordings of different respiratory and sympathetic motor outputs and of neuronal activity, and microinjections of agonists and antagonists in the ventral surface of the medulla oblongata. Moreover, in order to further elucidate the molecular mechanisms involved, we will also evaluate the phosphorylation of specific proteins of the RTN by the western blot technique. (AU)

Scientific publications
(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)
LEMES, EDUARDO V.; COLOMBARI, EDUARDO; ZOCCAL, DANIEL B. Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats. Journal of Applied Physiology, v. 121, n. 5, p. 1135-1144, NOV 1 2016. Web of Science Citations: 6.
LEMES, E. V.; AIKO, S.; ORBEM, C. B.; FORMENTIN, C.; BASSI, M.; COLOMBARI, E.; ZOCCAL, D. B. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats. ACTA PHYSIOLOGICA, v. 217, n. 3, p. 254-266, JUL 2016. Web of Science Citations: 10.

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