Neonatal Sympathoadrenal Response to Acute Hypoxia: Impairment after Experimental Intrauterine Growth Retardation

Abstract

ABSTRACT. Svm~athoadrenal svstem function mav be Abbreviations altered following i;trauterine 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 S D 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 by 3H-norepinephrine tracer and a-methyltyrosine techniques. Adrenal medullary catecholamine synthesis (CAT SYN) was measured by '4C-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 (Fioz = 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. (Pediatr Res 25:466-472, 1989)

Fetal growth restriction: adaptations and consequences

“…Thus, in contrast to acute hypoxaemia, placental restriction and the associated chronic hypoxaemia result in a suppression of the adrenaline synthetic capacity of the fetal adrenal medulla. Fetal growth restriction induced by single umbilical artery ligation in sheep (Oyama et al, 1992) results in a diminished fetal adrenaline response to delivery, and growth-restricted rat pups have impaired adrenaline secretory responses to acute hypoxia after birth (Shaul et al, 1989). Therefore, the impact of intrauterine hypoxaemia on adrenaline synthesis and secretion may have significant physiological consequences before, during and immediately after birth.…”

Neonatal Stress: Effects of Hypoglycemia and Hypoxia on Adrenal Tyrosine Hydroxylase Gene Expression

“…On the other hand, in the neonatal rat during the first week of life, hypoglycemic stress fails to result in significant CA release, as presynaptic nerve terminals are nonfunctional at that time (10)(11)(12)14,16). In contrast, at this same age neonatal hypoxia releases CA through a nonneurogenic mechanism, acting "directly7' on the adrenal medulla (11,14,(17)(18)(19). This suggests that the dual roles of transsynaptic activity (regulation of transmitter release and regulation of transmitter biosynthesis) may be functionally separated in the neonate.…”

Cerebral and Adrenal Monoamine Metabolism in the Growth-Retarded Rat Fetus under Normoxia and Hypoxia

“…Under hypoxia, AGA fetuses increased the tissue content of NE and E, probably as a result of the rate of synthesis increasing more than that of release (37). This response was not present in fetuses with IUGR in this study or in the rate neonate with IUGR in which synthesis and release were measured (37). Thus, these findings indicate a reduced capacity of the sympathoadrenal system in fetuses with IUGR to respond to hypoxic stress.…”

“…7). This could indicate an increased release in growthretarded fetuses (36), especially if synthesis rate is increased as in the growth-retarded rat neonate (37). Under hypoxia, AGA fetuses increased the tissue content of NE and E, probably as a result of the rate of synthesis increasing more than that of release (37).…”