Neonatal sympathoadrenal response to acute hypoxia: Impairment after experimental intrauterine growth retardation

Sympathoadrenal system function may be altered following intrauterine growth retardation (IUGR). We tested the hypothesis that the growth-retarded newborn rat pup has increased basal sympathoadrenal activity under normoxic conditions and a blunted sympathoadrenal response to acute hypoxia. IUGR was established by uterine artery ligation on d 18 of gestation in Sprague-Dawley rats. Growth-retarded pups were chosen as those whose birth wt was more than 2 x SD below the mean birth wt of control pups delivered to sham-operated dams. At 24 ± 12 h of age cardiac sympathetic neuronal activity (CSNA) was determined by³H-norepinephrine tracer and a-methyl-tyrosine techniques. Adrenal medullary catecholamine synthesis (CAT SYN) was measured by¹⁴C-tyrosine precursor methods, and adrenal catecholamine release (CAT REL) was determined using a-methyl-tyrosine. IUGR and control pups were studied over a 120-min period of normoxia or hypoxia (Fio₂ = 0.09). Under normoxic conditions, the IUGR pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to controls. Adrenal CAT REL in normoxic IUGR pups was selective for epinephrine. In response to acute hypoxia, control pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to normoxic controls, with the proportion of norepinephrine and epinephrine released mimicking the ratio of the two amines in the adrenal. In contrast, in hypoxic IUGR pups CSNA and adrenal CAT SYN did not increase, and norepinephrine alone was released from the adrenal medulla. It is speculated that IUGR in the rat may lead to an acceleration of cardiac sympathetic innervation and premature establishment of neural regulation of adrenomedullary function, resulting in impaired sympathoadrenal responses to acute stresses such as hypoxia. Compromised sympathoadrenal system function in the IUGR fetus or newborn may contribute to the pathogenesis of the perinatal morbidities and the increased perinatal mortality known to occur in this high risk population.