Woods L L, Ingelfinger J R, Nyengaard J R, Rasch R
Division of Nephrology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, Oregon 97201-3098, U.S.A.
Pediatr Res. 2001 Apr;49(4):460-7. doi: 10.1203/00006450-200104000-00005.
Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin-angiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 +/- 0.002 ng/mg, LP versus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 +/- 1 mm Hg, LP versus 126 +/- 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP versus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 +/- 0.16 10(6) microm(3), LP versus 1.11 +/- 0.10 10(6) microm(3), NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult.
在大鼠怀孕期间限制母体蛋白质摄入会导致其后代成年后出现高血压，但具体机制尚不清楚。我们的目的是确定这种成年期高血压是否可能是由于胎儿/新生儿肾素-血管紧张素系统（RAS）受抑制以及随之而来的肾单位数量减少而在发育过程中编程形成的。在整个妊娠期，给怀孕大鼠喂食正常蛋白质（19%，NP）或低蛋白质（8.5%，LP）饮食。LP幼崽的出生体重降低了13%（p<0.0005），且肾脏/体重比降低。新生LP幼崽的肾脏肾素mRNA水平显著降低；肾脏肾素浓度和肾素免疫染色受到抑制。新生LP幼崽的肾脏组织血管紧张素II水平也受到抑制（0.079±0.002 ng/mg，LP组对比0.146±0.016 ng/mg，NP组，p<0.01）。在有意识且长期植入仪器的成年后代（21周）中，LP组的平均动脉压更高（135±1 mmHg，LP组对比126±1 mmHg，NP组，p<0.00007），且LP组中以肾脏重量标准化的肾小球滤过率降低（p<0.04）。成年LP后代每只肾脏的肾小球数量较少（21,567±1,694，LP组对比28,917±2,342，NP组，p<0.03），且单个肾小球体积更大（1.81±0.16×10⁶μm³，LP组对比1.11±0.10×10⁶μm³，NP组，p<0.005）；每只肾脏所有肾小球的总体积无显著差异。因此，大鼠围产期蛋白质限制会抑制新生大鼠肾脏内的RAS，并导致成年后肾小球数量减少、肾小球增大和高血压。
