Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats

Davi J A Moraes,Benedito H Machado,Leni G H Bonagamba,Julian F R Paton,Melina P Da Silva

doi:10.1038/s41598-017-17113-7

Davi J A Moraes, Benedito H Machado + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-17113-7

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Abstract

Sympathetic activity displays rhythmic oscillations generated by brainstem inspiratory and expiratory neurons. Amplification of these rhythmic respiratory-related oscillations is observed in rats under enhanced central respiratory drive or during development of neurogenic hypertension. Herein, we evaluated the involvement of ventral medullary sympatho-excitatory catecholaminergic C1 neurons, using inhibitory Drosophila allatostatin receptors, for the enhanced expiratory-related oscillations in sympathetic activity in rats submitted to chronic intermittent hypoxia (CIH) and following activation of both peripheral (hypoxia) and central chemoreceptors (hypercapnia). Pharmacogenetic inhibition of C1 neurons bilaterally resulted in reductions of their firing frequency and amplitude of inspiratory-related sympathetic activity in rats in normocapnia, hypercapnia or after CIH. In contrast, hypercapnia or hypoxia-induced enhanced expiratory-related sympathetic oscillations were unaffected by C1 neuronal inhibition. Inhibition of C1 neurons also resulted in a significant fall in arterial pressure and heart rate that was similar in magnitude between normotensive and CIH hypertensive rats, but basal arterial pressure in CIH rats remained higher compared to controls. C1 neurons play a key role in regulating inspiratory modulation of sympathetic activity and arterial pressure in both normotensive and CIH hypertensive rats, but they are not involved in the enhanced late-expiratory-related sympathetic activity triggered by activation of peripheral or central chemoreceptors.

Highlights

It has long been recognized that vasoconstrictor class of sympathetic fibers show respiratory-related oscillations[1,2,3]
We found that C1 neurons projected to sympathetic preganglionic neurons in the thoracic (T8-T10) intermediolateral cell column (IML), as reflected by the distribution of varicosed axons intermingled with choline acetyltransferase (ChAT)-immunoreactive neurons (n = 4; Fig. 1C)
In in vivo and in situ preparations, acute inhibition of C1 neurons resulted in substantial reductions in arterial pressure, Traube-Hering waves, HR, in baseline and reflex-evoked inspiratory-related sympathetic activity recorded from C1 neurons and from postganglionic nerves

Summary

Introduction

It has long been recognized that vasoconstrictor class of sympathetic fibers show respiratory-related oscillations[1,2,3] This respiratory–sympathetic interaction underpins the production of rhythmic fluctuations in arterial pressure (Traube–Hering waves), which are derived from phasic constriction of the arterial tree[4,5,6]. We acutely silenced C1 neurons by application of the insect peptide allatostatin (Alst) following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila Alst receptor (AlstR)[26] in the RVLM of rats Using both in vivo (conscious) and in situ (arterially perfused brainstem preparations) rats, we determined the contribution of the C1 neuronal population for the generation of expiratory-modulated sympathetic activity of rats under enhanced central respiratory drive induced by either CIH or activation of peripheral or central chemoreceptors

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