Effect of Postnatal Maternal Protein Intake on Prenatal Programming of Hypertension

Abstract

This study examined whether postnatal maternal dietary protein deprivation during the time of nursing can program hypertension when the offspring are studied as adults. Rats were fed either a 6% or 20% protein diet during the second half of pregnancy and continued on the same diet while rats were nursing their pups. The neonates of all of the rats were cross-fostered to a different mother and studied as adults. Adult rats that had a normal prenatal environment but were reared by mothers fed a low-protein diet until weaning (20%-6%) were hypertensive, had a higher renal Naprotein abundance yet a comparable number of glomeruli, and had higher plasma renin and angiotensin II levels compared to control (20%-20%). Rats whose mothers were fed a 6% protein diet and cross-fostered to a different rat fed a 6% protein diet until weaning (6%-6%) were hypertensive, had elevated plasma renin and angiotensin II levels, and had a reduction in nephron number but had NKCC2 and NCC levels comparable to 20% to 20% offspring. The 6% to 20% had blood pressure and glomerular numbers comparable to 20% to 20% rats. The hypertension resulting from prenatal dietary protein deprivation can be normalized by improving the postnatal environment. Combined prenatal and postnatal maternal dietary protein deprivation and maternal dietary protein deprivation while nursing alone (20%-6%) results in hypertension, but the mechanism for the hypertension in these groups is different.

Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

“…Rats in the 20% to 6% group and 6% to 6% group did not gain weight at the same rate as rats in the 6% to 20% group and 20% to 20% group, which was still apparent in the present study when rats were studied at 3 and 17 mo of age. We also found that optimizing the postnatal environment by cross-fostering neonatal pups on day 1 of life whose mothers were fed a low-protein diet during pregnancy to a mother that was fed a 20% control diet during pregnancy and while nursing (6% to 20% group) prevented the reduction in nephron number (14,36). Only 6% to 6% rats had a decrease in nephron number (36).…”

“…We have previously examined the effect of cross-fostering rats whose mothers were fed a 6% protein diet and a 20% protein diet during pregnancy and while nursing (36). Offspring were weaned and fed a 20% diet and studied at 2 mo of age.…”

“…cause for the reduction in heart weight in the 6% group at 3 mo, although the weights were comparable at 17 mo (5). We have previously shown that cross-fostering a neonatal rat to a mother that was fed a 6% protein diet results in weight gain that is less than both 6% and 20% neonatal rats cross-fostered to a 20% mother (36). In our previous study, we studied rats until 2 mo of age, but, as shown here, 20% rats cross-fostered to a 6% mother and rats in the 6% to 6% group weighed less compared with the 20% to 20% group and the 6% to 20% group at 3 and 17 mo of age.…”

“…Thus, it is possible that postnatal insults in the rat may have a greater effect on renal function than prenatal insults. Indeed, we have recently shown that postnatal dietary deprivation during lactation results in hypertension (36). The purpose of the present study was to determine if prenatal programming results in a progressive decline in GFR and hypertension.…”

“…The second goal was to examine if improving the postnatal environment during the time of nephrogenesis prevents the decline in GFR and increase in blood pressure by crossfostering neonates from mothers that were fed a low-protein diet during pregnancy to mothers that were fed a normal protein diet. Finally, the third aim was to examine the effect of a maternal postnatal low-protein diet while nursing on rats whose mothers were fed a normal prenatal environment to determine if suboptimal postnatal nutrition, which causes failure to thrive (36), results in hypertension and a reduction in GFR in adult offspring.…”