Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis.
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 +/- 0.18 106 micro(3) in LLP vs. 2.01 +/- 0.14 106 micro(3) in NP). Female offspring showed qualitatively similar results.


CONCLUSIONS
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.
Woods
Lori L
LL
Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, Oregon 97239, USA. woodsl@ohsu.edu
Weeks
Douglas A
DA
Rasch
Ruth
R
D000375:Aging; D000818:Animals; D001794:Blood Pressure; D018753:Diet, Protein-Restricted; D005314:Embryonic and Fetal Development; D005260:Female; D005919:Glomerular Filtration Rate; D006128:Growth; D007668:Kidney / Q000196:embryology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D012727:Sex Characteristics