Prenatal programming of adult blood pressure: role of maternal corticosteroids.
Both maternal glucocorticoid administration and maternal dietary protein or food restriction in pregnancy cause fewer nephrons and hypertension in the adult offspring. The purpose of these studies was to determine the extent to which nutritional factors contribute to programming of offspring hypertension by maternal glucocorticoids. Pregnant rats were treated with dexamethasone (100 microg x kg(-1) x d(-1) sc) on days 1-10 (ED) or days 15-20 (LD) of pregnancy. Additional groups of pregnant animals were pair fed to the early (EDPF) and late (LDPF) dexamethasone-treated groups, and another group was untreated or given vehicle (C). The dams treated with dexamethasone reduced their food intake and lost or failed to gain a normal amount of weight during treatment; body weights of ED dams caught up to normal after the treatment period, whereas those of LD dams did not. In adulthood ( approximately 21 wks), chronically instrumented male offspring of ED had normal blood pressures (125 +/- 2 mmHg vs. 126 +/- 1 mmHg in C), whereas LD offspring were hypertensive (136 +/- 3 mmHg). However, LDPF offspring were equally hypertensive (134 +/- 2 mmHg). Glomerular filtration rates normalized to body weight were not significantly different among groups. Qualitatively similar results were found in female offspring. Thus the long-term effects of maternal glucocorticoid administration at this dose on offspring's blood pressure may, in large part, be accounted for by the reduction in maternal food intake. These data suggest that maternal glucocorticoids and maternal food or protein restriction may, at least in part, share a common mechanism in programming offspring for hypertension. The window of sensitivity of future offspring blood pressure to either maternal insult coincides with nephrogenesis in the rat, suggesting that impaired renal development could play an important role in this programming.
Woods
Lori L
LL
Division of Nephrology and Hypertension, L463, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239-3098, USA. woodsl@ohsu.edu
Weeks
Douglas A
DA
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005260:Female; D007668:Kidney / Q000196:embryology* / Q000502:physiology*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000305:Adrenal Cortex Hormones; D003907:Dexamethasone