Am. J. Respir. Crit. Care Med., Vol 149, No. 2, Feb 1994, 392-399.
Adenosine-induced bronchoconstriction in conscious hyperresponsive and sensitized guinea pigs
JR Thorne and KJ Broadley
Department of Pharmacology, Welsh School of Pharmacy, University of Wales Cardiff, United Kingdom.
Inhaled adenosine induces bronchoconstriction in asthmatic and allergic
subjects but not in nonasthmatics. This study examined the responses of
conscious guinea pigs in which antigen sensitization is induced by
ovalbumin pretreatment and airway hyperresponsiveness to carbachol is
induced by exposure to ozone and platelet-activating factor-acether (PAF).
Airway responses to aerosol challenge with carbachol or adenosine were
determined as the change in specific airway conductance (SGaw) measured by
whole-body plethysmography. In untreated animals, carbachol (20
micrograms/ml, 60 s) induced a rapid fall in SGaw (peak, 18 +/- 5% at 5
min) indicative of bronchoconstriction, whereas adenosine (1 mg/ml, 60 s)
caused an increase in SGaw (34 +/- 8% at 15 min). Animals pretreated with
ovalbumin displayed similar responses to carbachol (14 +/- 5% at 5 min) as
control animals and were therefore sensitized but not hyperresponsive.
However, adenosine (1 mg/ml) caused a rapid bronchoconstriction, peaking at
20 min (25 +/- 5%). Exposure of animals to nebulized PAF-acether (10
micrograms/ml) for 60 s produced a bronchoconstriction, which peaked at 10
min (18 +/- 7%) and returned to basal levels by 60 min. Similarly, exposure
to ozone (1.4 ppm) for 60 min caused bronchoconstriction (peak at 20 min,
19 +/- 6%), with recovery after 1 h. Both PAF- and ozone-exposed animals
displayed significant hyperresponsiveness to carbachol administered 1 h
from the end of the exposure period. The peak bronchoconstrictor responses
before and after PAF exposure were 10 +/- 9 and 28 +/- 4%, and responses
before and after ozone exposure were 22 +/- 5 and 61 +/- 9%.(ABSTRACT
TRUNCATED AT 250 WORDS)
