Welch W J, Wilcox C S, Thomson S C
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Semin Nephrol. 1999 May;19(3):251-62.
Glomerular filtration is closely coupled to tubular reabsorption by a system of tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus (JGA) of each nephron, where changes are sensed in the salt content of fluid at the luminal macula densa and that information is transmitted to the glomerular microvasculature to elicit compensatory changes in single nephron glomerular filtration rate (GFR). Type I nitric oxide synthase (NOS) is expressed in the macula densa. Other NOS isoforms may be produced in the mesangium, and glomerular microvessels. These NOSs are strategically positioned to influence each step of the TGF process. However, micropuncture experiments using NOS antagonists have shown that nitric oxide (NO) does not mediate TGF. Instead, local NOS blockade causes the curve that represents TGF to shift leftward and become more steep. Changes in macula densa NO production may underlie the resetting of TGF, which is required in order to keep the TGF curve aligned with ambient tubular flow as tubular flow changes to accommodate physiologic circumstances. Also, macula densa NO production may be substrate limited and dissociated from NOS protein content. The importance of NO to TGF resetting and the substrate dependence of NO production have both been found during changes in dietary salt.
肾小球滤过通过肾小管-肾小球反馈（TGF）系统与肾小管重吸收紧密耦联。TGF在每个肾单位的球旁器（JGA）内发挥作用，在管腔致密斑处的液体盐含量变化被感知，该信息被传递至肾小球微血管，以引发单个肾单位肾小球滤过率（GFR）的代偿性变化。I型一氧化氮合酶（NOS）在致密斑中表达。其他NOS同工型可能在系膜和肾小球微血管中产生。这些NOS的位置有利于影响TGF过程的每一步。然而，使用NOS拮抗剂的微穿刺实验表明，一氧化氮（NO）并不介导TGF。相反，局部NOS阻断会使代表TGF的曲线向左移动并变得更陡峭。致密斑NO生成的变化可能是TGF重置的基础，为使TGF曲线在肾小管流量变化以适应生理情况时与周围肾小管流量保持一致，这是必需的。此外，致密斑NO生成可能受底物限制，且与NOS蛋白含量无关。在饮食盐变化期间，已发现NO对TGF重置的重要性以及NO生成的底物依赖性。
