Maternal glucocorticoids and prenatal programming of hypertension

Abstract

Maternal glucocorticoids have been postulated to play an important role in prenatal programming for adult hypertension in the offspring. However, we have shown previously that offspring hypertension caused by maternal dexamethasone subcutaneous administration at 100 μg·kg−1·day−1can be accounted for by the corresponding reduction in food intake that these mothers experience. The present studies were designed to determine whether there is a lower dose of dexamethasone that does not reduce maternal food intake yet still causes hypertension in the adult offspring. Pregnant rats were treated with subcutaneous dexamethasone at 50 (D50) or 25 (D25) μg·kg−1·day−1on days 15–20 of pregnancy. An additional group was untreated or received vehicle injections (control). D25 and D50 dams reduced their food intake by 17% during and after treatment and gained 31% less weight than control over the course of gestation. In adulthood (∼21 wk), chronically instrumented male offspring of D50 and D25 had normal blood pressures (D50: 131 ± 2 mmHg and D25: 127 ± 3 mmHg vs. 127 ± 2 mmHg in control). Qualitatively similar results were found in female offspring. Thus neither dexamethasone per se at these doses nor the accompanying modest reductions in maternal food intake and weight gain have blood pressure programming effects. As far as has been tested, there does not appear to be a dose of dexamethasone that, given over this time period in the rat, programs offspring hypertension without reducing maternal food intake and weight gain. These data do not support the hypothesis that maternal glucocorticoids program offspring hypertension directly.