Dworkin L D, Feiner H D
J Clin Invest. 1986 Mar;77(3):797-809. doi: 10.1172/JCI112377.
Micropuncture and/or morphologic studies were performed in intact Wistar-Kyoto rats (WKY) (group 0), intact spontaneously hypertensive rats (SHR) (groups 1 and 5), uninephrectomized (UNX) WKY (groups 2 and 6), and UNX SHR (groups 3 and 4, 7 and 8). UNX was performed when rats were 5 wk of age. Groups 0-4 were observed for 34 wk after which whole kidney clearance and morphologic studies were performed. Groups 5-8 underwent micropuncture study at 10 wk of age. Groups 4 and 8 were fed a diet containing 6% protein. All other rats ingested standard laboratory diet. 5 wk after UNX, normotensive group 6 had higher single nephron glomerular filtration rate (SNGFR) and initial glomerular plasma flow rate (QA) than intact, hypertensive group 5. Glomerular transcapillary hydraulic pressure difference (delta P) was similar in these two groups. Hypertensive group 7 exhibited less elevation in SNGFR and QA than group 6, but delta P was significantly increased. The presence of glomerular capillary hypertension in UNX SHR at 10 wk was associated with the development of significant proteinuria and an increased incidence of mesangial expansion and glomerular sclerosis at 7 mo (group 3) as compared with groups 0, 1, and 2. Protein restriction prevented the development of increased delta P in UNX SHR (group 8) and also conferred long-term protection from increased urinary protein excretion and glomerular injury (group 4). These studies suggest that glomerular capillary hypertension predisposes to glomerular injury in this model of hypertension with reduced renal mass.
在完整的Wistar-Kyoto大鼠(WKY)(0组)、完整的自发性高血压大鼠(SHR)(1组和5组)、单侧肾切除(UNX)的WKY(2组和6组)以及UNX的SHR(3组和4组、7组和8组)中进行了微穿刺和/或形态学研究。大鼠5周龄时进行单侧肾切除。0-4组观察34周,之后进行全肾清除率和形态学研究。5-8组在10周龄时进行微穿刺研究。4组和8组喂食含6%蛋白质的饮食。所有其他大鼠摄入标准实验室饮食。单侧肾切除后5周,血压正常的6组单肾单位肾小球滤过率(SNGFR)和初始肾小球血浆流速(QA)高于完整的高血压5组。这两组的肾小球跨毛细血管液压差(δP)相似。高血压7组的SNGFR和QA升高幅度小于6组,但δP显著增加。与0组、1组和2组相比,10周龄的UNX SHR中肾小球毛细血管高血压的存在与7个月时显著蛋白尿的发生以及系膜扩张和肾小球硬化发生率增加相关(3组)。蛋白质限制可防止UNX SHR中δP升高(8组),还可长期预防尿蛋白排泄增加和肾小球损伤(4组)。这些研究表明,在这种肾质量减少的高血压模型中,肾小球毛细血管高血压易导致肾小球损伤。