Hypoxic response in newborn rat is attenuated by neurokinin-1 receptor blockade.
Substance P (SP) is considered to be involved in the regulation of respiration, in particular when respiratory demands are increased, such as during hypoxic stress. In the present study we have investigated the effects of intracerebroventricular pre-treatment with the selective NK-1 receptor antagonist RP67580 on the respiratory response to hypoxia in 5-day-old rat pups. Basal respiration was not altered by RP67580. When subjected to hypoxia (10% O(2)), rat pups pre-treated with RP67580 were unable to sustain the increased respiratory frequency at 10 min. In situ hybridisation demonstrated increased expression of c-fos mRNA in several brainstem areas following hypoxia. This activation was blocked by the antagonist in the retrotrapezoid nucleus and the rostral ventrolateral medulla, areas known to be involved in the hypoxic ventilatory response. This study corroborates a role of endogenously released SP, mediated via NK-1 receptors, in the sustained response to hypoxia in 5-day-old rat pups and suggests that neurons in the rostral ventrolateral medulla are important in this function. It also represents a further example that neuropeptides are released under stressful conditions.
Wickström
H Ronny
HR
Department of Woman and Child Health, Karolinska Institutet, 17177 Stockholm, Sweden. ronny.wickstrom@kbh.ki.se
Berner
Jonas
J
Holgert
Hans
H
Hökfelt
Tomas
T
Lagercrantz
Hugo
H
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001933:Brain Stem / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D007211:Indoles / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D054833:Isoindoles; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000502:physiology
D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P