ROLE OF GLUCOCORTICOIDS IN PROGRAMMING OF MATERNAL DIET-INDUCED HYPERTENSION IN THE RAT

A rat model of hypertension induced by in utero exposure to maternal l ow protein diets has previously been described. Low protein exposed ra t pups ar of lower weight at birth and have large associated placentas . Such animals are proposed, therefore, to mirror individuals in the h uman population perceived to be at greater risk of cardiovascular dise ase in adulthood. Recent work has suggested that maternal glucocortico ids may programme this increased risk of later disease. The role of gl ucocorticoids in programming the hypertensive state was assessed by ad ministration of the 11 beta-hydroxylase inhibitor, metyrapone, to preg nant rats consuming 18 (control) or 9% (low protein) casein diets. At day 14 of pregnancy, fetuses and placentas of low protein-fed rat were significantly larger than those of controls. Metyrapone significantly inhibited corticosterone synthesis in both dietary groups, and attenu ated the more rapid growth of fetus and placenta in the low protein fe d group. Systolic blood pressures of rats exposed to the low protein d iet in utero were significantly high (29 mm Hg) than those exposed to the control diet. Metyrapone abolished the hypertensive state of low p rotein exposed rats, but in the control group significantly elevated b lood pressure by 15 mm Hg. Maternal and fetal glucocorticoid interacti ons in utero clearly have an important role in determining future regu lation of blood pressure. Maternal-diet induced hypertension in the ra t would appear to be a glucocorticoid-dependent phenomenon.