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 compared contractile responses of airway tissue from fetal, newborn and young adult guinea pigs to cumulative doses of both BAY K 8644 and CGP 28392 under isometric conditions in vitro. Responses were examined in the presence and absence of aspirin to determine if endogenous cyclooxygenase products modulated these effects. BAY K 8644 generated a contractile response in 85 of 86 tissues. Maximum contraction was greater in extrathoracic tracheas from newborns when compared to adults (P < .05). In fetuses and newborns, contraction overall was greater in the presence of aspirin; however, in adult airways cyclooxygenase blockade did not appear to have any effect (P < .05). In contrast, CGP 28392 produced no contraction in 14 of 19 tracheas (all ages combined) in the presence of aspirin; whereas, all 18 tracheas in the absence of aspirin contracted. Also, there were no significant differences in maximum response among these age groups or tissue types to CGP 28392. Increased sensitivity of tracheas in immature guinea pigs was observed for both drugs in the absence of aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
Pichoff
B E
BE
Department of Pediatrics, Tripler Army Medical Center, Honolulu, Hawaii.
Uyehara
C F
CF
Nakamura
K T
KT
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004336:Drug Antagonism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development; D009130:Muscle, Smooth / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology
D002120:Calcium Channel Agonists; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D001241:Aspirin