Ventilatory responses to acute hypoxia in neurokinin-1 receptor deficient mice.
The regulatory effect of substance P on respiration is mediated via neurokinin (NK) receptors. While previous studies suggest that NK-1 receptors are involved, little is known about the role NK-2 receptors in ventilatory responses to hypoxia. Ventilatory responses to acute hypoxia (8% O2 in N2) were measured by indirect plethysmography in unanaesthetized, unrestrained NK-1 receptor gene deficient (NK-1-/-) and wild-type mice. In additional experiments mice were treated with an NK-2 receptor antagonist prior to hypoxic challenge. Resting ventilatory parameters were not different between groups. NK-1-/- mice displayed significantly greater shortening of expiratory time and higher increase of breathing frequency during hypoxia than wild-type mice. Treatment with the NK-2 receptor antagonist SR 48968 (1 mg/kg) resulted in a further shortening of inspiratory and expiratory time in NK-1-/- but not wild-type mice. These results demonstrate that both NK-1 and NK-2 receptors are involved in the modification of ventilation in response to acute hypoxia.
Grasemann
Hartmut
H
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. hartmut.grasemann@sickkids.ca
Gerard
Norma P
NP
De Sanctis
George T
GT
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage; D005260:Female; D000860:Hypoxia / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010880:Piperidines / Q000008:administration & dosage; D010991:Plethysmography / Q000379:methods; D018040:Receptors, Neurokinin-1 / Q000172:deficiency*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012119:Respiration / Q000187:drug effects / Q000235:genetics*
D001549:Benzamides; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C073839:SR 48968