Do catecholamines contribute to the effects of neonatal hypoxia on development of brain and heart? Influence of concurrent alpha-adrenergic blockade on ornithine decarboxylase activity.
Hypoxia in the neonate releases catecholamines from the adrenal medulla, a response which is necessary to survive. This study examines whether a similar dependence exists for the ability of brain and heart tissue to recover from hypoxia-induced damage, as assessed by measurements of ornithine decarboxylase (ODC) activity. Hypoxia at either 1 day or 8 days of age produced a subsequent elevation of brain ODC which persisted for 1 week, a pattern known to be associated with recovery from tissue damage and delayed cellular maturation. Pretreatment of the rats with phenoxybenzamine, an alpha-receptor blocking agent, resulted in attenuation of the long-term ODC response, but did not interfere with effects on the enzyme during the hypoxia itself. In the heart, hypoxia at 8 days of age displayed similar effects, with long-term ODC elevations which were attenuated by phenoxybenzamine. Hypoxia at 1 day of age also produced long-term heart ODC stimulation, but in this case the effect was exacerbated by phenoxybenzamine, an effect consistent with the greater dependence of cardiac tissue on alpha-receptor-mediated responses to hypoxia at that age. These results suggest that alpha-receptor stimulation by catecholamines released during neonatal hypoxia play a role in the metabolic adjustment of brain and heart tissue to damage and may aid in subsequent recovery.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Orband-Miller
L
L
Queen
K L
KL
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D009955:Ornithine Decarboxylase