MAINTENANCE OF MATERNAL DIET-INDUCED HYPERTENSION IN THE RAT IS DEPENDENT ON GLUCOCORTICOIDS

Recent epidemiological evidence suggests that adult cardiovascular ris k is determined by birth weight and factors that influence birth weigh t, such as maternal nutrition. Data from animal models suggest that an interaction between nutrition and glucocorticoid hormones ''programs' ' increased risk of adult hypertension. Increased fetal exposure to ma ternal glucocorticoids that is proposed to occur from a reduction in t he placental barrier to maternal glucocorticoid, 11 beta-hydroxysteroi d dehydrogenase, is suggested to program hypertension in the resultant offspring from both glucocorticoid-treated and maternally protein-res tricted rats. The extent to which postnatal glucocorticoid stimulation may influence the progression of hypertension in the offspring from p rotein-restricted rat darns was assessed in 6-week-old male Wistar rat s, prenatally exposed to either an 18% casein (control) or 9% casein ( low protein) diet. Rats from each dietary group were sham operated, ad renalectomized or adrenalectomized, and treated with 20 mg corticoster one/kg body weight per day. Before surgery, systolic blood pressure wa s significantly higher in the low protein-exposed rats compared with c ontrols (165+/-3.8 versus 142+/-3.3 mm Hg, P<.0001). Adrenalectomy of the low protein-exposed animals significantly reduced the blood pressu re to control levels, while corticosterone replacement restored the hy pertensive state. No effect of adrenalectomy on blood pressure was obs erved in 18% casein controls. In both dietary groups adrenalectomy dec reased brain, but not hepatic, glucocorticoid-sensitive enzyme activit ies and corticosterone treatment elevated activities of all enzymes. T he data suggest that maternal diet-induced hypertension is dependent o n an intact adrenal gland postnatally and that glucocorticoids are key trophic agents in maintaining the high blood pressure.