Strain dependence of the airway response to dry-gas hyperpnea challenge in the rat.
The aim of the study was to investigate strain dependence and mechanisms of airway responses to dry-gas hyperpnea challenge in the rat. We studied responses in a strain that is hyperresponsive to methacholine, Fischer 344 (F-344); in two normoresponsive strains, Lewis and ACI; and in an atopic but normoresponsive strain, Brown Norway (BN). We examined the effects of a neurokinin (NK) 1-receptor (CP-99994), an NK2-receptor (SR-48968), and a leukotriene D4 (LTD4)-receptor antagonist (pranlukast) on responses to hyperpnea challenge in BN rats. The animals were ventilated with a tidal volume of 8 ml/kg and a frequency of 150 breaths/min with either a dry or humidified mixture of 5% CO2-95% O2 for 5 min for hyperpnea challenge, whereas responses to challenge were measured during spontaneous breathing. Pulmonary resistance increased after dry-gas challenge in BN and ACI but not in F-344 and Lewis rats. CP-99994, SR-48968, and pranlukast significantly attenuated the increase in pulmonary resistance after dry-gas challenge. There were no significant differences in responsiveness to airway challenge with LTD4 among the BN, F-344 and ACI rats. We conclude that responses to dry-gas hyperpnea challenge are strain dependent in rats and are mediated by NKs and LTD4.
Yang
X X
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Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada H2X 2P2.
Powell
W S
WS
Xu
L J
LJ
Martin
J G
JG
D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology; D017998:Leukotriene D4 / Q000378:metabolism / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000502:physiology*; D013045:Species Specificity
D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D017998:Leukotriene D4