Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat.

Hypertension is strongly predicted by a low birthweight:placental weight ratio. Two independent models have been described to explain this association; less than optimal maternal protein nutrition leading to fetal undernutrition, or glucocorticoid excess. Pregnant rats were fed diets containing 18 per cent casein (control) or 9 per cent casein, balanced for energy. On day 20 of gestation the pregnancies were terminated and placentae collected for determination of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity. Placental 11 beta HSD normally protects the fetus from the effects of maternal glucocorticoids. Activity was specifically attenuated by mild protein restriction (33 per cent in activity), whilst activities of glucocorticoid-insensitive control enzymes were unchanged and glucocorticoid-inducible glutamine synthetase activity was increased (27 per cent), relative to activity in placentae from control animals. The nutritional manipulation during pregnancy significantly increased systolic blood pressure (17 mmHg) in the resulting offspring in early adulthood. A possible common pathway whereby maternal environmental factors may influence fetal and placental growth and programme disease is inferred.