Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide.
Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide.
复制标题
大鼠肾小管肾小球反馈系统的研究。
DOI：
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发表时间：
1978
影响因子：
15.9
通讯作者：
R. Blantz
中科院分区：
文献类型：
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作者：
B. J. Tucker;R. Steiner;L. Gushwa;R. Blantz
苯甲酰胺（一种在近端小管中具有主要抑制作用的碳酸酐酶抑制剂）给药后，浅表肾单位肾小球滤过率（sngfr）降低的具体机制，已通过测量相关压力、流量和肾小球通透性在贫水的Munich-Wistar大鼠（一种具有表面肾小球的品系）中进行了研究。由于苯甲酰胺降低近端绝对重吸收率，肾小管液向远端肾单位的输送率至少应短暂增加，并可通过激活肾小管-肾小球反馈系统降低sngfr。苯甲酰胺（第1组）后，Sngfr从29.2+/2.0降至2.1+/3.1 nl/min（P <0.01），下降百分比等于肾小球滤过率，与远端小管收集物中获得的sngfr相似。单独的研究（第2组）显示，如果在对照前通过在近端小管中插入长油块来防止远端肾单位递送的短暂增加，则sngfr的降低被阻止（30.3+/1.0 vs. 30.3+/1.8 nl/min，P> 0.9）。在同一大鼠的成对“未阻断”肾单位中，第2组的sngfr下降（33.0+/1.0 vs. 25.2+/2.3 nl/min，P <0.01）。在阻止sngfr减少的“阻塞”肾单位中，液体离开近端小管的速率从16.9+/1.0 nl/min增加到23.1+/1.0 nl/min（P <0.01）。在第1组研究中，sngfr下降且未阻止近端小管最后一段流出的流量（远端输送）的一过性增加（约等于8 nl/min），苯甲酰胺未改变稳态远端输送（13.9+/1.1 vs. 14.2+/2.2 nl/min）。此外，当近端油块放置15 min且苯甲酰胺给药后远端递送速率降低时，sngfr恢复至对照、苯甲酰胺给药前值，这表明该激活是可逆的。这些数据表明，激活肾小管-肾小球反馈的短暂增加远端交付是负责减少sngfr。对肾小球超滤的所有决定因素的分析显示，苯甲酰胺治疗后导致sngfr降低的传出机制是肾单位血浆流量降低（101+/13 vs. 66+/13 nl/min，P <0.01）。静水压和肾小球通透性系数并没有导致苯甲酰胺引起的sngfr降低。由于尽管sngfr和绝对近端重吸收率都发生了很大的变化，但远端递送的速率保持恒定，因此建议远端递送的速率可能是由肾小管-肾小球反馈系统通过sngfr的改变来调节的生理实体。
The specific mechanism whereby superficial nephron glomerular filtration rate (sngfr) is reduced after the administration of benzolamide, a carbonic anhydrase inhibitor with a primary inhibitory effect in the proximal tubule, have been examined by measuring pertinent pressures, flows, and glomerular permeabilities in the hydropenic Munich-Wistar rat, a strain with surface glomeruli. Because benzolamide decreases absolute proximal reabsorptive rate, the rate of delivery of tubular fluid to the distal nephron should be at least transiently increased and may reduce sngfr by activating the tubulo-glomerular feedback system. Sngfr fell from 29.2+/2.0 to 2.1+/3.1 nl/min (P less than 0.01) after benzolamide (group 1), a percentage reduction equal to kidney glomerular filtration rate and similar to sngfr obtained in collections from distal tubules. Separate studies (group 2) revealed that if transient increases in distal nephron delivery were prevented by insertion of a long oil block in proximal tubules before control, the decrease in sngfr was prevented (30.3+/1.0 vs. 30.3+/1.8 nl/min, P greater than 0.9). In paired "unblocked" nephrons in the same rats, sngfr fell in group 2 (33.0+/1.0 vs. 25.2+/2.3 nl/min, P less than 0.01). In "blocked" nephrons in which sngfr reduction was prevented, the rate of fluid leaving the proximal tubule increased from 16.9+/ to 23.1+/1.0 nl/min (P less than 0.01). In group 1 studies in which sngfr fell and transient increases in flow out of the last segment of the proximal tubule (distal delivery) (approximately equal to 8 nl/min) were not prevented, steady-state distal delivery was unchanged by benzolamide (13.9+/1.1 vs. 14.2+/2.2 nl/min). Also, sngfr returned toward control, pre-benzolamide values, when a proximal oil block was placed for 15 min and the rate of distal delivery reduced after benzolamide administration, which suggests that this activation was reversible. These data suggest that activation of tubulo-glomerular feedback by transient increases in distal delivery was responsible for decreases in sngfr. Analysis of all determinants of glomerular ultra-filtration revealed that the efferent mechanism leading to reduced sngfr after benzolamide was decreased nephron plasma flow (101+/13 vs. 66+/13 nl/min, P less than 0.01). Hydrostatic pressure and the glomerular permeability coefficient did not contribute to reductions in sngfr with benzolamide. Because the rate of distal delivery remained constant in spite of large changes in both sngfr and absolute proximal reabsorptive rate, it is suggested that the rate of distal delivery may be the physiologic entity that is regulated by the tubulo-glomerular feedback system via alterations in sngfr.