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% oR²0% protein diet to inhibit glucocorticoid production and compared the offspring to rats that were the product of mothers fed either a 6% oR²0% protein diet during the last half of pregnancy. Results Male offspring from the 6% group had elevated systolic blood pressure (149±2 vs. 130±5mmHg, 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±5mmHg). 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.