Woods L L, Weeks D A, Rasch R
Division of Nephrology, Hypertension, and Clinical Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
Hypertension. 2001 Sep;38(3):337-42. doi: 10.1161/01.hyp.38.3.337.
The present study was designed to determine whether adult hypertension caused by a reduced number of nephrons from birth is due to preceding glomerular damage. Newborn male Sprague-Dawley rat pups were uninephrectomized during the first 24 hours after birth (UNX rats). At 20 weeks of age, chronically instrumented UNX animals were hypertensive on a normal-sodium (0.20%) diet compared with sham-operated controls (142+/-2 versus 124+/-2 mm Hg in controls). Body weights and the total kidney-to-body weight ratio were not significantly different in adult UNX animals compared with controls. Glomerular filtration rate (GFR) was reduced by 49% in UNX rats (1.85+/-0.24 versus 3.65+/-0.22 mL/min). Urine protein excretions were higher in UNX rats (20+/-2 versus 7+/-1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28+/-9 versus 3+/-1 mm Hg). In contrast, in animals studied at 8 weeks of age, GFR was only reduced by 26% in UNX animals (2.02+/-0.06 versus 2.73+/-0.07 mL/min). Their hypertension (125+/-2 versus 117+/-2 mm Hg) was also salt sensitive (increase on high-sodium diet of 35+/-11 versus 8+/-2 mm Hg in controls) but was not associated with proteinuria or histological signs of glomerular disease. Number of glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50% of the nephrons, when done during development, causes reduced renal function and salt-sensitive hypertension in adulthood. Hypertension is present earlier in life than signs of glomerular disease, which suggests that hypertension is a major contributor to rather than primarily resulting from onset of renal disease.
本研究旨在确定出生时肾单位数量减少所致的成人高血压是否归因于先前的肾小球损伤。新生雄性斯普拉格 - 道利大鼠幼崽在出生后的头24小时内接受单侧肾切除术（UNX大鼠）。在20周龄时，与假手术对照组相比，长期植入仪器的UNX动物在正常钠（0.20%）饮食下出现高血压（对照组为124±2 mmHg，UNX组为142±2 mmHg）。与对照组相比，成年UNX动物的体重和肾脏与体重的总比值无显著差异。UNX大鼠的肾小球滤过率（GFR）降低了49%（1.85±0.24对3.65±0.22 mL/分钟）。UNX大鼠的尿蛋白排泄量更高（对照组为7±1 mg/天，UNX组为20±2 mg/天）。在高钠（3.15%）饮食下，UNX动物的动脉压升高幅度大于对照组（28±9对3±1 mmHg）。相比之下，在8周龄时研究的动物中，UNX动物的GFR仅降低了26%（2.02±0.06对2.73±0.07 mL/分钟）。它们的高血压（125±2对117±2 mmHg）对盐也敏感（高钠饮食时升高，对照组为8±2 mmHg，UNX组为35±11 mmHg），但与蛋白尿或肾小球疾病的组织学迹象无关。UNX动物每只肾脏的肾小球数量与对照组无差异，但单个肾小球体积增加了41%。因此，在发育过程中手术切除50%的肾单位会导致成年期肾功能降低和盐敏感性高血压。高血压在生命早期就出现，早于肾小球疾病的迹象，这表明高血压是肾脏疾病发生的主要促成因素，而非主要由肾脏疾病引发。
