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| Author(s): |
Darlan da Silva Bazilio
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2022-03-19 |
| Examining board members: |
Benedito Honório Machado;
Ana Carolina Takakura Moreira;
Helio Cesar Salgado;
Daniel Breseghello Zoccal
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| Advisor: | Benedito Honório Machado |
| Abstract | |
The peripheral chemoreflex is activated by a reduction in O2 partial pressure in arterial blood (PaO2) and its responses include bradycardia (parasympathoexcitation), arterial pressure elevation (sympathoexcitation), tachypnea, and active expiration. The first synapse of the chemoreceptor afferents occurs in the commissural region of the nucleus tractus solitarius (NTS), one of the main nuclei in the brainstem responsible for sensory integration and cardiorespiratory control. Studies from our laboratory have shown the participation of glial cells, via glutamatergic and purinergic mechanisms, in the modulation of neural pathways in the NTS involved in autonomic and respiratory control. Studies from our laboratory have also showed that, in rats of the Wistar-Ribeirão Preto strain (WRP), sustained hypoxia (SH, FiO2=0.1 for 24 hours) produces sympathetic overactivity, arterial pressure elevation and increased ventilation, along with increased intrinsic excitability and excitatory neurotransmission in NTS neurons, possibly due to glial dysfunction in the NTS. In the first part of the present study, we performed a characterization of the effects of HM on the cardiovascular and respiratory patterns of rats from the Wistar Hanover (WH) and Sprague Dawley (SD) strains. In response to SH, SD rats showed cardiovascular and respiratory changes similar to those observed in WRP rats, whereas WH rats were less sensitive to these changes. Thus, in the second part of this study we performed in situ working heart-brainstem preparations, which allows recording of autonomic and respiratory motor outputs, to evaluate the possible involvement of glial cells in the modulation of peripheral chemoreflex neural pathways in the commissural NTS of control and SH rats from the SD strain. We also evaluated the participation of glutamatergic and purinergic mechanisms in the processing autonomic and respiratory chemoreflex responses in the commissural NTS. For that, we performed bilateral microinjections of fluorocitrate (FCt, glial cell metabolic inhibitor), KYN (non-selective ionotropic glutamatergic receptor antagonist) and PPADS (P2 purinergic receptor antagonist) into the anterior caudal region of the commissural NTS and performed peripheral chemoreflex activations with potassium cyanide at various time points within a 60-min time window. Microinjections of FCt into the NTS did not produce significant changes in baseline autonomic and respiratory patterns or in respiratory and sympathoexcitatory responses to peripheral chemoreflex activation in control or SH rats, although they produced a significant reduction in bradycardic responses after 45 and 60 minutes in SH-exposed rats. Under baseline conditions, the reduction in expiratory duration produced by the simultaneous antagonism of glutamatergic and purinergic receptors in the NTS was attenuated in HM rats in relation to control rats. Similarly, microinjections of FCt attenuated the reduction in expiratory duration provoked by the simultaneous antagonism of these receptors in the NTS in control rats, but did not produce further reduction in HM rats. Furthermore, metabolic inhibition of glial cells did not produce any additional effect to the simultaneous antagonism of glutamatergic and purinergic receptors in the NTS with respect to the autonomic and respiratory responses to peripheral chemoreflex activation in control and SH rats, which were all significantly reduced by the simultaneous antagonism in the NTS. The results of the present work indicate a combined role of glutamatergic and purinergic receptors in the commissural NTS in processing chemoreflex autonomic and respiratory responses in control and SH rats and an involvement of NTS glial cells in modulating baseline respiratory activity generation in both control and SH rats, as well as in modulating the parasympathetic component of the chemoreflex in SH rats. (AU) | |
| FAPESP's process: | 19/21328-0 - Participation of astrocytes in the modulation of NTS neurons involved in the processing of cardiovascular and respiratory components of the chemoreflex of rats submitted to maintained hypoxia |
| Grantee: | Darlan da Silva Bazilio |
| Support Opportunities: | Scholarships in Brazil - Doctorate |