Pre- and post-inspiratory neurons change their firing properties in female rats exposed to chronic intermittent hypoxia

Author(s)

Souza, George M. P. R. ^[1] ; Barnett, William H. ^{[2, 3]} ; Amorim, Mateus R. ^[1] ; Lima-Silveira, Ludmila ^[1] ; Moraes, Davi J. A. ^[1] ; Molkov, I, Yaroslav ; Machado, Benedito H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Physiol, Sch Med Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] I, Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 - USA

^[3] I, Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 - USA

• Document type: Journal article
• Source: Neuroscience; v. 406, p. 467-486, MAY 15 2019.
• Web of Science Citations: 0

Abstract

Obstructive sleep apnea patients face episodes of chronic intermittent hypoxia (CIH), which has been suggested as a causative factor for increased sympathetic activity (SNA) and hypertension. Female rats exposed to CIH develop hypertension and exhibit changes in respiratory-sympathetic coupling, marked by an increase in the inspiratory modulation of SNA. We tested the hypothesis that enhanced inspiratory-modulation of SNA is dependent on carotid bodies (CBs) and are associated with changes in respiratory network activity. For this, in CIH-female rats we evaluated the effect of CBs ablation on respiratory-sympathetic coupling, recorded from respiratory neurons in the working heart-brainstem preparation and from NTS neurons in brainstem slices. CIH-female rats had an increase in peripheral chemoreflex response and in spontaneous excitatory neurotransmission in NTS. CBs ablation prevents the increase in inspiratory modulation of SNA in CIH-female rats. Pre-inspiratory/inspiratory (Pre-I/I) neurons of CIH-female rats have a reduced firing frequency. Post-inspiratory neurons are active for a longer period during expiration in CIH-female rats. Further, using the computational model of a brainstem respiratory-sympathetic network, we demonstrate that a reduction in Pre-I/I neuron firing frequency simulates the enhanced inspiratory SNA modulation in CIH-female rats. We conclude that changes in respiratory-sympathetic coupling in CIH-female rats is dependent on CBs and it is associated with changes in firing properties of specific respiratory neurons types. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/06077-5 - Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia
• Grantee: Benedito Honorio Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/06550-8 - Neural mechanisms involved in the generation of arterial hypertension in female rats submitted to chronic intermittent hypoxia
• Grantee: George Miguel Perbone Robuste Souza
• Support Opportunities: Scholarships in Brazil - Doctorate