Airway and tissue behaviour during the early response in sensitized
brown-norway rats: role of serotonin and leukotriene d4.
Nagase, T., M. J. Dallaire, and M. S. Ludwig.
Meakins-Christie Laboratories and Royal Victoria Hospital, McGill
University, Montreal, Quebec, Canada
APStracts 2:0461A, 1995.
We have recently demonstrated that tissue resistance increases during
the early response (ER) to antigen challenge in sensitized Brown
-Norway (BN) rats. The purpose of the present study was to investigate
the role of the potential ER mediators, serotonin (5-HT) and
leukotriene D4 (LTD4) in the airway and tissue response. We
sensitized BN rats with ovalbumin (OA) and performed experiments in
anesthetized, open-chested, mechanically ventilated (f = 1Hz, VT = 12
ml/kg, PEEP = 3 cmH2O) animals. We affixed alveolar capsules to the
lungs to measure alveolar pressure and calculated the resistance of
lung (RL), tissue (Rti) and airway (Raw). In order to assess the
effects of LTD4 and 5-HT we administered the antagonists,
methysergide (5-HT antagonist) and MK-571 (LTD4 antagonist) prior to
challenge. To assess lung morphometry during the ER, the lungs of 4
animals from each group were frozen with liquid nitrogen (PEEP = 3
cmH2O). Airway constriction was assessed by measuring the ratio of
the airway lumen to the ideally relaxed airway (Abm/Abm*). Tisuue
distortion was assessed by measuring the mean linear intercept
between alveolar walls (Lm), an atelectasis index (ATI) derived by
calculating the ratio of tissue/airspace, and the standard deviation
(SD) of the two. In all animals receiving OA but no antagonists an ER
was seen (RL, Rti, Raw = 180.7+6.1, 155.4+8.2, 223.1+14.0 % baseline,
respectively). Methysergide significantly inhibited the ER (RL, Rti,
Raw = 117.0+5.9, 101.2+1.6, 133.7+10.2 %), while MK-571 partially
reduced the ER (RL, Rti, Raw = 144.2+5.6, 132.9+5.7, 155.5+9.2 %).
Abm/Abm* was significantly decreased and SDLm and SDATI were
significantly increased in animals receiving OA alone and in those
receiving MK-571 prior to OA challenge. These data suggest that
alterations in both airways and tissues contribute to the ER and that
serotonin, and, to a lesser degree, LTD4, are important mediators of
the ER in this rat model of extrinsic asthma.
Received 21 February 1995; accepted in final form 27 September
1995.
APS Manuscript Number A202-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95