Daugharty T M, Ueki I F, Mercer P F, Brenner B M
J Clin Invest. 1974 Jan;53(1):105-16. doi: 10.1172/JCI107527.
An experimental model of postischemic, acute renal failure has been developed in Wistar rats with surface glomeruli, thereby making possible a direct assessment of the mechanisms responsible for the fall in glomerular filtration rate that characterizes this disorder. Whole kidney and cortical single nephron filtration rates were reduced proportionately, on average by approximately 40%, after 3 h of nearly complete occlusion of the ipsilateral renal artery. The possibility of a significant transtubular leak of inulin was excluded. This decline in filtration rate occurred in the absence of measured changes in mean arterial pressure, mean glomerular transcapillary hydrostatic pressure, or net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary. Net ultrafiltration pressure at the efferent end of the capillary approached zero both before and after ischemic injury, demonstrating that filtration pressure equilibrium was achieved throughout this study. Single nephron filtration fraction remained unchanged, indicating that the fall in filtration rate was accompanied by a proportional decline in glomerular plasma flow. The results indicate that the fall in filtration rate was solely the consequence of this fall in glomerular plasma flow. Since filtration rate per nephron is equal to the product of the ultrafiltration coefficient and mean ultrafiltration pressure, this product must also have fallen in proportion to the decline in glomerular plasma flow. Evidence is presented to indicate that a change in ultrafiltration coefficient is not required to account for the observed fall in filtration rate. The reduction in glomerular plasma flow, occuring in the absence of a concomitant decline in mean glomerular capillary hydrostatic pressure, resulted from large and proportional increases in afferent and efferent arteriolar resistances. These resistance changes appear to play a fundamental role in the pathogenesis of this form of acute renal failure.
在具有浅表性肾小球的Wistar大鼠中建立了缺血后急性肾衰竭的实验模型，从而能够直接评估导致该疾病特征性肾小球滤过率下降的机制。在同侧肾动脉几乎完全闭塞3小时后，全肾和皮质单肾单位滤过率平均成比例降低，约40%。菊粉显著跨肾小管泄漏的可能性被排除。滤过率的下降发生在平均动脉压、平均肾小球跨毛细血管静水压或肾小球毛细血管入球端和出球端的净超滤压未出现可测变化的情况下。缺血损伤前后，毛细血管出球端的净超滤压均接近零，表明在整个研究过程中实现了滤过压平衡。单肾单位滤过分数保持不变，表明滤过率的下降伴随着肾小球血浆流量的成比例下降。结果表明，滤过率的下降完全是肾小球血浆流量下降的结果。由于每个肾单位的滤过率等于超滤系数与平均超滤压的乘积，该乘积也必然与肾小球血浆流量的下降成比例下降。有证据表明，不需要超滤系数的变化来解释观察到的滤过率下降。肾小球血浆流量的减少，在平均肾小球毛细血管静水压没有相应下降的情况下发生，是由于入球小动脉和出球小动脉阻力大幅且成比例增加所致。这些阻力变化似乎在这种形式的急性肾衰竭的发病机制中起基本作用。
