TY - JOUR
T1 - Programming of adult blood pressure by maternal protein restriction
T2 - Role of nephrogenesis
AU - Woods, Lori L.
AU - Weeks, Douglas A.
AU - Rasch, Ruth
N1 - Funding Information:
The authors thank Nabiel Azar, Nathan Beget, Kathryn Parent, Melinda Davison, and Birgitte Grann for technical assistance. These studies were supported by grants P01HD34430 from the National Institute of Child Health and Human Development and R01HL70132 from the National Heart, Lung and Blood Institute, a Grant-in-Aid from the American Heart Association, a grant from the March of Dimes Birth Defects Foundation, and a grant from the Danish Diabetes Association.
PY - 2004/4
Y1 - 2004/4
N2 - Background. Modest maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult male but not female offspring. This study determined whether a more severe protein restriction has equivalent effects on male and female rat offspring, and examined the role of nephrogenesis in this programming. Methods. Sprague-Dawley rats were fed a protein-restricted (5% protein) diet throughout (LLP), or during the first (LLP/NP) or second (NP/LLP) half of pregnancy. Controls ate a normal diet (NP, 19% protein). Adult offspring were chronically instrumented at 22 weeks; glomerular number and volume were estimated using stereologic techniques. Results. Mean arterial pressures in male offspring were significantly higher in LLP (136 ± 2 mm Hg) or NP/LLP (137 ± 2 mm Hg) than in LLP/NP (125 ± 1 mm Hg) or NP (125 ± 2 mm Hg). Moreover, the hypertension was salt-sensitive (increase of 16 ± 4 mm Hg in LLP on a high Na+ diet compared to 2 ± 2 mm Hg in NP). Glomerular number (per kidney) was reduced (15,400 ± 2,411 in LLP vs. 27,208 ± 1,534 in NP) but average individual glomerular volume was not different (1.98 ± 0.18106 μ3 in LLP vs. 2.01 ± 0.14 10 6 μ3 in NP). Female offspring showed qualitatively similar results. Conclusion. Severe maternal dietary protein restriction reduces glomerular number and programs for salt-sensitive adult hypertension in both female and male offspring. The window of sensitivity of adult blood pressure to prenatal protein restriction falls within the period of nephrogenesis in the rat. These data are consistent with the hypothesis that maternal protein restriction causes adult hypertension in the offspring through impairment of renal development.
AB - Background. Modest maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult male but not female offspring. This study determined whether a more severe protein restriction has equivalent effects on male and female rat offspring, and examined the role of nephrogenesis in this programming. Methods. Sprague-Dawley rats were fed a protein-restricted (5% protein) diet throughout (LLP), or during the first (LLP/NP) or second (NP/LLP) half of pregnancy. Controls ate a normal diet (NP, 19% protein). Adult offspring were chronically instrumented at 22 weeks; glomerular number and volume were estimated using stereologic techniques. Results. Mean arterial pressures in male offspring were significantly higher in LLP (136 ± 2 mm Hg) or NP/LLP (137 ± 2 mm Hg) than in LLP/NP (125 ± 1 mm Hg) or NP (125 ± 2 mm Hg). Moreover, the hypertension was salt-sensitive (increase of 16 ± 4 mm Hg in LLP on a high Na+ diet compared to 2 ± 2 mm Hg in NP). Glomerular number (per kidney) was reduced (15,400 ± 2,411 in LLP vs. 27,208 ± 1,534 in NP) but average individual glomerular volume was not different (1.98 ± 0.18106 μ3 in LLP vs. 2.01 ± 0.14 10 6 μ3 in NP). Female offspring showed qualitatively similar results. Conclusion. Severe maternal dietary protein restriction reduces glomerular number and programs for salt-sensitive adult hypertension in both female and male offspring. The window of sensitivity of adult blood pressure to prenatal protein restriction falls within the period of nephrogenesis in the rat. These data are consistent with the hypothesis that maternal protein restriction causes adult hypertension in the offspring through impairment of renal development.
KW - Fetal origins of adult disease
KW - Gender
KW - Glomerular filtration rate
KW - Nephron number
KW - Renal plasma flow
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U2 - 10.1111/j.1523-1755.2004.00511.x
DO - 10.1111/j.1523-1755.2004.00511.x
M3 - Article
C2 - 15086473
AN - SCOPUS:1642545187
SN - 0085-2538
VL - 65
SP - 1339
EP - 1348
JO - Kidney International
JF - Kidney International
IS - 4
ER -