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 mmHg) than in LLP/NP (125 +/- 1 mmHg) or NP (125 +/- 2 mm Hg). Moreover, the hypertension was salt-sensitive (increase of 16 +/- 4 mmHg 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 10(6) mu(3) in LLP vs. 2.01 +/- 0.14 10(6) mu(3) 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.