Evidence that prenatal programming of hypertension by dietary protein deprivation is mediated by fetal glucocorticoid exposure.
BACKGROUND
Prenatal programming by maternal dietary protein deprivation and prenatal dexamethasone result in a reduction in nephron number and hypertension when the offspring are studied as adults.


METHODS
To determine whether prenatal dietary protein deprivation results in a reduction in nephron number and hypertension in offspring by exposure to maternal glucocorticoids, we administered metyrapone to rats fed either a 6% or 20% protein diet to inhibit glucocorticoid production and compared the offspring to rats that were the product of mothers fed either a 6% or 20% protein diet during the last half of pregnancy.


RESULTS
Male offspring from the 6% group had elevated systolic blood pressure (149 ± 2 vs. 130 ± 5 mm Hg, P < 0.05) and a reduction in glomeruli compared to the 20% group (22,111 ± 627 vs. 29,666 ± 654 glomeruli/kidney, P < 0.001). Maternal metyrapone administration did not affect the blood pressure in the 20% group but ameliorated the increase in blood pressure in the 6% male group to values comparable to the 20% control group (138 ± 6 vs. 130 ± 5 mm Hg). Male offspring of the 6% group that received metyrapone had an increase in the number of glomeruli compared to the vehicle-treated 6% group (26,780 ± 377 vs. 22,111 ± 627 glomeruli/kidney, P < 0.001), but less glomeruli compared to the 20% protein control group (26,780 ± 377 vs. 29,666 ± 654 glomeruli/kidney, P = 0.01).


CONCLUSIONS
The reduction in nephron number and hypertension induced by maternal protein deprivation in male offspring is ameliorated by inhibition of glucocorticoid production.
Habib
Sabeen
S
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, USA.
Gattineni
Jyothsna
J
Twombley
Katherine
K
Baum
Michel
M
D000818:Animals; D001794:Blood Pressure; D003907:Dexamethasone / Q000633:toxicity*; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000473:pathology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D003907:Dexamethasone; D008797:Metyrapone