Prenatal exposure to propranolol via continuous maternal infusion: effects on physiological and biochemical processes mediated by beta adrenergic receptors in fetal and neonatal rat lung.
During lung development, beta adrenergic receptors undergo transient coupling to enzymes and physiological processes which govern respiratory function and trophic responses to neural stimulation. To determine the role of endogenous catecholamines in mediating these processes, we examined the gestational and postnatal effects of chronic propranolol infusion (10 mg/kg/day) throughout fetal development. The effectiveness of receptor blockade in dam and fetus were confirmed through measurements of heart rate and enzymatic stimulatory responses to acute challenge with beta agonists (terbutaline to isoproterenol). Propranolol antagonized the ability of terbutaline to stimulate fetal lung fluid resorption and phosphatidic acid phosphatase, a key enzyme in surfactant synthesis. After birth, basal lung compliance and the compliance response to beta adrenergic stimulation were compromised in the neonates that had been exposed to propranolol before birth, despite the fact that direct receptor antagonism had disappeared by that time. After weaning, animals exposed to prenatal propranolol showed interference with basal activity of ornithine decarboxylase (an enzyme involved in transduction of neuronal and hormonal trophic stimuli) and its response to acute beta adrenergic challenge. These results suggest that endogenous fetal catecholamines participate in perinatal respiratory adaptation to air-breathing and help to program future cellular responsiveness to neuronal input.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
Navarro
H A
HA
Eylers
J P
JP
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D004247:DNA / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008170:Lung Compliance / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D009955:Ornithine Decarboxylase / Q000032:analysis; D010711:Phosphatidate Phosphatase / Q000032:analysis; D011247:Pregnancy; D011433:Propranolol / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D004247:DNA; D011433:Propranolol; D010711:Phosphatidate Phosphatase; D009955:Ornithine Decarboxylase