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Locus coeruleus noradrenergic neurons and CO2 drive to breathing

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Abstract

The Locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. In the present study, we assessed the role of LC noradrenergic neurons in the cardiorespiratory and thermal responses to hypercapnia. To selectively destroy LC noradrenergic neurons, we administered 6-hydroxydopamine (6-OHDA) bilaterally into the LC of male Wistar rats. Control animals had vehicle (ascorbic acid) injected (sham group) into the LC. Pulmonary ventilation (plethysmograph), mean arterial pressure (MAP), heart rate (HR), and body core temperature (T c, data loggers) were measured followed by 60 min of hypercapnic exposure (7% CO2 in air). To verify the correct placement and effectiveness of the chemical lesions, tyrosine hydroxylase immunoreactivity was performed. Hypercapnia caused an increase in pulmonary ventilation in all groups, which resulted from increases in respiratory frequency and tidal volume (V T) in sham-operated and 6-OHDA-lesioned groups. The hypercapnic ventilatory response was significantly decreased in 6-OHDA-lesioned rats compared with sham group. This difference was due to a decreased V T in 6-OHDA rats. LC chemical lesion or hypercapnia did not affect MAP, HR, and T c. Thus, we conclude that LC noradrenergic neurons modulate hypercapnic ventilatory response but play no role in cardiovascular and thermal regulation under resting conditions.

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Acknowledgments

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We thank Gustavo Michel, Camila Linhares Taxini, and Euclides Roberto Secato for excellent technical assistance and Dr. Mogens Glass for critically reading this manuscript. Vivian Biancardi was the recipient of a FAPESP graduate scholarship (05/56129-5).

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  1. Department of Animal Morphology and Physiology, Sao Paulo State University—UNESP FCAV, Jaboticabal, SP, Brazil

    Vivian Biancardi, Kênia C. Bícego & Luciane H. Gargaglioni

  2. Department of Zoology, Sao Paulo State University—UNESP, Rio Claro, SP, Brazil

    Maria Camila Almeida

  3. Departamento de Morfologia e Fisiologia Animal, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista Júlio de Mesquita Filho, Via de acesso Paulo Donato Castellane s/n, 14870-000, Jaboticabal, SP, Brasil

    Luciane H. Gargaglioni

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  1. Vivian Biancardi
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Correspondence to Luciane H. Gargaglioni.

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Biancardi, V., Bícego, K.C., Almeida, M.C. et al. Locus coeruleus noradrenergic neurons and CO2 drive to breathing. Pflugers Arch - Eur J Physiol 455, 1119–1128 (2008). https://doi.org/10.1007/s00424-007-0338-8

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