Respiratory control in neonatal mice with NADPH oxidase deficiency.
A membrane bound cytochrome b(558) (NADPH oxidase) is a candidate for the oxygen sensor in pulmonary neuroepithelial bodies (NEBs) - putative airway chemoreceptors. Recent electrophysiological studies on NEB from mice with NADPH oxidase deficiency (OD; gp(91phox) knock-out) have shown lack of response of O(2) sensitive K(+) current to hypoxia challenge compared with wild-type (WT) control mice. To assess the effects of oxidase deficiency on the control of ventilation at the whole animal level, respiratory measurements were conducted under normoxic and hypoxic conditions in neonatal OD mice and compared that with the WT control group. Five-day-old OD mice were faster and shallower breathers during normoxia as well as hypoxia. In addition, the maximum hypoxic ventilatory response of the OD mice was lower than that of the WT control group and the peak increase in minute ventilation (.V(max)-.V(normoxia)) was greater in WT control than the OD mice (P=0.02). Since the lung development and NEB morphology in OD mice were comparable to the WT control mice, the observed differences implicate NADPH oxidase as an O(2) sensor involved in neonatal ventilatory control, possibly modulated via pulmonary NEBs.
Kazemian
P
P
Department of Pediatric Laboratory Medicine, Division of Pathology, The Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada M5G 1X8.
Stephenson
R
R
Yeger
H
H
Cutz
E
E
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000294:innervation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D010991:Plethysmography; D012143:Respiratory Physiological Phenomena; D013990:Tidal Volume
D019255:NADPH Oxidases; D010100:Oxygen