Neonatal nutritional deprivation or enhancement: the cardiac-sympathetic axis and its role in cardiac growth and stress responses.
To determine the mechanisms by which neuronal input influences cardiac growth during altered neonatal nutritional status, rats were reared in small, standard, or large litter sizes and the adrenergically mediated stimulation of cardiac ornithine decarboxylase was determined; ornithine decarboxylase provides a mechanistic link connecting adrenergic input to cardiac growth. Nutritionally deprived pups showed impaired development of sympathetic reflex stimulation as shown by the attenuation of the cardiac ornithine decarboxylase response to hydralazine-induced hypotension throughout the preweanling period. The subnormal reactivity to hydralazine reflected a defect in neurotransmission, as a full response was obtained with direct beta-receptor stimulation (isoproterenol). Nevertheless, cardiac hypertrophy in response to repeated isoproterenol administration was markedly suppressed in nutritionally deprived animals, suggesting that the beta-receptor/ornithine decarboxylase pathway had become uncoupled from growth. Because maturation of neural connections to peripheral tissues causes a loss of hypoxia tolerance, nutritional status also influenced the ability of neonatal rats to survive hypoxia. These data indicate that cardiac growth suppression or enhancement caused by nutritional manipulations may be mediated, in part, through alterations in the development of neuronal input to the tissue, and that similar factors influence survival during hypoxic stress.
Bell
J M
JM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Whitmore
W L
WL
Slotkin
T A
TA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006321:Heart / Q000187:drug effects / Q000254:growth & development* / Q000294:innervation; D006830:Hydralazine / Q000494:pharmacology; D000860:Hypoxia / Q000401:mortality; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009752:Nutritional Status; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*
D006830:Hydralazine; D009955:Ornithine Decarboxylase; D007545:Isoproterenol