Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis

Abstract

BACKGROUND: Hypertension and coronary heart disease are programmed by maternal undernutrition in utero. The feeding of low-protein diets to rats during their pregnancy results in higher blood pressure in the offspring from the age of weaning. OBJECTIVE: To determine whether a low-protein diet increases foetal exposure to glucocorticoids of maternal origin, resulting in altered hypothalamic-pituitary-adrenal axis function and hypertension. DESIGN: Rats were fed an 18% casein diet (control) or a 9% casein diet (low protein) during pregnancy. Low-protein-fed dams were injected with metyrapone to inhibit corticosterone synthesis or with metyrapone plus a replacement dose of corticosterone. The offspring of these pregnancies had their blood pressure determined when they were aged 7 weeks. METHODS: The systolic blood pressure was determined using an indirect tail-cuff method. Glucocorticoid action in the hypothalamus was measured using glycerol-3 phosphate dehydrogenase as a reference enzyme. RESULTS: Blood pressures of rats exposed to maternal low-protein diets in utero were elevated significantly relative to those of control rats. The animals that had been exposed to a maternal low-protein diet also exhibited increased glycerol-3 phosphate dehydrogenase (GPDH) activity in the hypothalamus, whereas their pyruvate kinase activity was not changed. The offspring of rats injected with metyrapone did not have raised blood pressure or GPDH activities. Replacement of corticosterone during pregnancy had no effect upon the blood pressures and GPDH activities of male offspring, but it reversed the effects of metyrapone in female offspring. CONCLUSIONS: Exposure to a maternal low-protein diet in utero programmes hypertension in the rat. The data are consistent with the hypothesis that corticosteroids of maternal origin play a role in this programming effect.