EFFECT OF CALCIUM AGONISTS, BAY-K-8644 AND CGP-28392, ON GUINEA-PIG AIRWAY SMOOTH-MUSCLE FUNCTION DURING DEVELOPMENT

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.