Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, 92161, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 Jan 1;302(1):R75-83. doi: 10.1152/ajpregu.00357.2011. Epub 2011 Sep 21.
Tubuloglomerular feedback (TGF) stabilizes nephron function from minute to minute and adapts to different steady-state inputs to maintain this capability. Such adaptation inherently renders TGF less efficient at buffering long-term disturbances, but the magnitude of loss is unknown. We undertook the present study to measure the compromise between TGF and TGF adaptation in transition from acute to chronic decline in proximal reabsorption (Jprox). As a tool, we blocked proximal tubule sodium-glucose cotransport with the SGLT2 blocker dapagliflozin in hyperglycemic rats with early streptozotocin diabetes, a condition in which a large fraction of proximal fluid reabsorption owes to SGLT2. Dapagliflozin acutely reduced proximal reabsorption leading to a 70% increase in early distal chloride, a saturated TGF response, and a major reduction in single nephron glomerular filtration rate (SNGFR). Acute and chronic effects on Jprox were indistinguishable. Adaptations to 10-12 days of dapagiflozin included increased reabsorption by Henle's loop, which caused a partial relaxation in the increased tone exerted by TGF that could be explained without desensitization of TGF. In summary, TGF contributes to long-term fluid and salt balance by mediating a persistent decline in SNGFR as the kidney adapts to a sustained decrease in Jprox.
管球反馈（TGF）可稳定每分钟的肾单位功能，并适应不同的稳态输入以维持这种能力。这种适应本质上使 TGF 缓冲长期干扰的效率降低，但损失的程度尚不清楚。我们进行了本研究，以测量 TGF 和 TGF 适应之间的权衡，以从近端重吸收（Jprox）的急性到慢性下降过渡。作为一种工具，我们用 SGLT2 阻断剂达格列净阻断高血糖大鼠的近端小管钠-葡萄糖共转运，这种情况是 SGLT2 负责近端液体重吸收的一个很大比例。达格列净急性减少近端重吸收，导致早期远端氯增加 70%，达到 TGF 饱和反应，单肾单位肾小球滤过率（SNGFR）大幅降低。急性和慢性对 Jprox 的影响无法区分。达格列净治疗 10-12 天的适应包括 Henle 袢的重吸收增加，这导致 TGF 施加的增加张力部分松弛，而无需 TGF 脱敏即可解释这种松弛。总之，TGF 通过介导 SNGFR 的持续下降，在肾脏适应 Jprox 持续下降的过程中，有助于长期的液体和盐平衡。
