Regulation of neonatal rat lung compliance by beta-adrenergic receptor stimulation: effects of prenatal exposure to terbutaline or dexamethasone.
beta-Adrenergic receptor stimulation is thought to participate in the perinatal switchover of the lung to air-breathing. In the current study, we have determined whether prenatal exposure of rats to terbutaline (10 mg/kg on gestational days 17,18 and 19) exerts promotional effects on lung function solely through its immediate actions at beta-receptors or whether terbutaline influences subsequent reactivity to adrenergic stimuli; we have contrasted the effects with those seen with a glucocorticoid (dexamethasone, 0.8 mg/kg on gestational days 17, 18 and 19). On postnatal day 3, basal lung compliance and lung rupture volumes were reduced after treatment with either terbutaline or dexamethasone, effects related primarily to drug-induced growth retardation; these effects were not present if data were corrected for relative tissue size. Despite a slightly reduced basal compliance, prenatal terbutaline exposure markedly enhanced postnatal reactivity to acute challenge with isoproterenol. In contrast, dexamethasone primarily enhanced basal compliance (corrected for weight deficits), with only minor effects on the isoproterenol response. These results suggest that, rather than producing classical receptor desensitization, gestational exposure to a beta-agonist sensitizes lung compliance to postnatal beta-receptor stimulation. Promotional effects of terbutaline on neonatal lung function are thus distinct from functional changes achieved with glucocorticoids, such as dexamethasone.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013726:Terbutaline / Q000494:pharmacology*
D003907:Dexamethasone; D007545:Isoproterenol; D013726:Terbutaline