HYPERTENSION INDUCED BY FETAL EXPOSURE TO A MATERNAL LOW-PROTEIN DIET, IN THE RAT, IS PREVENTED BY PHARMACOLOGICAL BLOCKADE OF MATERNAL GLUCOCORTICOID SYNTHESIS

Background Hypertension and coronary heart disease are programmed by m aternal undernutrition in utero. The feeding of low-protein diets to r ats during their pregnancy results in higher blood pressure in the off spring from the age of weaning. Objective To determine whether a low-p rotein diet increases foetal exposure to glucocorticoids of maternal o rigin, resulting in altered hypothalamic-pituitary-adrenal axis functi on and hypertension, Design Rats were fed an 18% casein diet (control) or a 9% casein diet (low protein) during pregnancy, Low-protein-fed d ams were injected with metyrapone to inhibit corticosterone synthesis or with metyrapone plus a replacement dose of corticosterone. The offs pring of these pregnancies had their blood pressure determined when th ey were aged 7 weeks, Methods The systolic blood pressure was determin ed using an indirect tail-cuff method. Glucocorticoid action in the hy pothalamus 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 tho se of control rats. The animals that had been exposed to a maternal lo w-protein diet also exhibited increased glycerol-3 phosphate dehydroge nase (GPDH) activity in the hypothalamus, whereas their pyruvate kinas e activity was not changed. The offspring of rats injected with metyra pone did not have raised blood pressure or GPDH activities. Replacemen t of corticosterone during pregnancy had no effect upon the blood pres sures and GPDH activities of male offspring, but it reversed the effec ts of metyrapone in female offspring, Conclusions Exposure to a matern al low-protein diet in utero programmes hypertension in the rat. The d ata are consistent with the hypothesis that corticosteroids of materna l origin play a role in this programming effect.