Be. Pichoff et al., EFFECT OF CALCIUM AGONISTS, BAY-K-8644 AND CGP-28392, ON GUINEA-PIG AIRWAY SMOOTH-MUSCLE FUNCTION DURING DEVELOPMENT, The Journal of pharmacology and experimental therapeutics, 265(2), 1993, pp. 524-528
Dihydropyridine calcium agonists affect airway smooth muscle function
by modulating the voltage-dependent calcium channel. Two such agonists
, BAY K 8644 and CGP 28392 increase airway smooth muscle tone in adult
guinea pigs but their actions during ontogeny are unknown. We compare
d contractile responses of airway tissue from fetal, newborn and young
adult guinea pigs to cumulative doses of both BAY K 8644 and CGP 2839
2 under isometric conditions in vitro. Responses were examined in the
presence and absence of aspirin to determine if endogenous cyclooxygen
ase products modulated these effects. BAY K 8644 generated a contracti
le response in 85 of 86 tissues. Maximum contraction was greater in ex
trathoracic tracheas from newborns when compared to adults (P < .05).
In fetuses and newborns, contraction overall was greater in the presen
ce of aspirin; however, in adult airways cyclooxygenase blockade did n
ot appear to have any effect (P < .05). In contrast, CGP 28392 produce
d no contraction in 14 of 19 tracheas (all ages combined) in the prese
nce of aspirin; whereas, all 18 tracheas in the absence of aspirin con
tracted. Also, there were no significant differences in maximum respon
se among these age groups or tissue types to CGP 28392. Increased sens
itivity of tracheas in immature guinea pigs was observed for both drug
s in the absence of aspirin. Our results demonstrate: 1) BAY K 8644 ap
pears to produce greater maximal contractions; 2) BAY K 8644 shows dif
ferences in airway smooth muscle contraction with respect to age of gu
inea pig, tracheobronchial segment used and whether aspirin was presen
t or not; 3) CGP 28392, while producing airway smooth muscle contracti
on in the absence of exogenous contractile agents, is almost completel
y without contractile activity in the presence of aspirin; and 4) feta
l and newborn extrathoracic trachea in the absence of aspirin are more
sensitive to BAY K 8644 and CGP 28392 than young adults.