The role of tachykinins in sulfur dioxide-induced
bronchoconstriction in anesthetized guinea pigs.
Hajj, Ahmad M., Nausherwan K. Burki, and Lu-Yuan Lee, Ahmad M. Hajj,
Nausherwan K. Burki and Lu-Yuan Lee.
Department of Physiology and Department of Medicine, Division of
Pulmonary and Critical Care Medicine, University of Kentucky,
Lexington, Kentucky 40536, U.S.A.
APStracts 3:0064A, 1996.
To investigate the role of tachykinin release in mediating the
bronchoconstrictive effect of sulfur dioxide (SO2) inhalation,
measurements of dynamic lung compliance (Cdyn), total pulmonary
resistance (RL), and arterial blood pressure (ABP) were made in
anesthetized guinea pigs. Brief exposure (6 tidal breaths) to SO2 at
concentrations between 500 to 2,000 ppm resulted in a concentration
-dependent increase in RL, decrease in Cdyn, and systemic hypotension.
For example, SO2 at 2,000 ppm induced reversible and reproducible
changes in RL, Cdyn and ABP of +1041 +/- 234 %, -60 +/- 6 %, and
-25.8 +/- 4.3 % of the baseline values, respectively. Pretreatment
with two selective neurokinin (NK)-1 and NK-2 receptor antagonists,
CP-99,994 and SR-48,968, resulted in almost complete inhibition of
the increase in RL and of the decrease in Cdyn, while preserving the
decrease in ABP. Antagonism of the NK-2 receptor alone resulted in
inhibition of the majority of the SO2-induced bronchoconstriction,
while that of the NK-1 and muscarinic receptors did not have a
significant effect. We conclude that the release of tachykinins from
sensory endings plays a central role in SO2-induced
bronchoconstriction in anesthetized guinea pigs, primarily via the
activation of the NK-2 receptor.
Received 30 August 1995; accepted in final form 12 January 1996.
APS Manuscript Number A949-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96