Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla.
Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60-90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P < 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.
Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
T Luise
TL
King
David D
DD
Kline
Brian C
BC
Ruyle
Cheryl M
CM
Heesch
Eileen M
EM
Hasser
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines
Fos; blood pressure; catecholaminergic neurons; chemoreflex; retrograde label