Maternal glucocorticoids and prenatal programming of hypertension.
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 microg x kg(-1) x day(-1) can 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) microg x kg(-1) x day(-1) on 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 ( approximately 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.
Woods
Lori L
LL
Division of Nephrology and Hypertension, L463, Oregon Health and Science Univ., 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239-3098, USA. woodsl@ohsu.edu
D000818:Animals; D001724:Birth Weight / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids; D003907:Dexamethasone