Adrenocortical activity in the newborn spontaneously hypertensive rat

Abstract

Blood pressure is reportedly elevated in the spontaneously hypertensive rat (SHR) neonate, the etiology of which remains unclear. Aberrations in the hypothalamic-pituitary-adrenal axis have been implicated, as it is well accepted that excess corticosteroids are associated with hypertension. We examined aspects of adrenocortical activity in the neonatal SHR 1 to 21 days old and its normotensive genetic control, the Wistar-Kyoto rat (WKY). We found a fourfold greater abundance of P450scc mRNA in adrenals of SHR versus WKY day 1 neonates, and increasing but comparable abundance of adrenal P450c11 B mRNA on neonatal days 1 to 21. The pattern of P450c11AS mRNA expression was distinctly different in the adrenals of SHR and WKY neonates; the relative abundance of this mRNA in SHR increased 15-fold over the 21-day period examined, whereas that in WKY remained fairly stable. RT-PCR for the presence/abundance of adrenal P450c11B3 mRNA showed absence in day 1 SHR and WKY, comparable abundances on neonatal days 7 and 14, and a distinctly greater abundance in the day 21 SHR adrenals. Peripheral corticosterone levels were threefold greater in the day 1 SHR neonate; aldosterone levels were elevated in both the SHR and WKY day 1 neonate. Thereafter, corticosterone and aldosterone levels were comparable on days 7, 14, and 21, although the anticipated depression in circulating corticosterone levels typical of the stress hyporesponsive period was noted in both SHR and WKY neonates. Although patterns of adrenocortical activity differ in the newborn SHR and WKY rat, our findings do not support an etiologic role for corticosteroids in the reported hypertension of the SHR. However, observed differences in corticosteroid profiles may augment or have a permissive effect upon the etiologic factor(s).