Inhibition of local nitric oxide synthase increases homeostatic efficiency of tubuloglomerular feedback.
Inhibition of local nitric oxide synthase increases homeostatic efficiency of tubuloglomerular feedback.
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抑制局部一氧化氮合酶可提高肾小管肾小球反馈的稳态效率。
DOI：
10.1152/ajprenal.1995.269.6.f892
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Thomson,S
中科院分区：
文献类型：
--
作者：
Vallon,V;Thomson,S
肾单位滤过率（SNGFR）和近端肾小管重吸收是通过肾小球反馈（TGF）和肾小球平衡（GTB）过程协调的。我们通过微穿刺将 NO 合酶抑制剂 NG-单甲基-L-精氨酸 (L-NMMA) 输送到 Inactin 麻醉的正常血容量大鼠的晚期近端肾单位中，研究了一氧化氮 (NO) 在 TGF 和 GTB 中的作用。首先，我们确定了在阻塞性蜡块下游亨利氏环的顺行微灌注期间 SNGFR 对晚期近端肾小管流速 (VLP) 的依赖性（开环微灌注）。其次，我们通过扰动自由流动的肾单位中的 VLP 来检查 TGF-GTB 系统的稳态效率（即其稳定 VLP 的能力），同时使用非侵入性光学技术测量扰动（闭环扰动）上游的流量。第三，我们测试了L-NMMA是否可以通过改变开环微灌注期间VLP与早期远端肾小管液体的流速（VED）或离子含量（CED）之间的关系来改变TGF的传入信号。在开环微灌注过程中，L-NMMA 将 VLP 处的 SNGFR 降低至 10 至 40 nl/min，但不会改变 VLP 与 VED 或 CED 之间的关系。在闭环扰动期间，L-NMMA 不会影响周围的 VLP，但会增加 TGF-GTB 系统的稳态效率。对 SNGFR 和环境 VLP 的综合影响表明 L-NMMA 减少近端重吸收。然而，这只能解释稳态效率增加的一小部分，其中更大的部分必须在球旁装置内介导。似乎肾小球旁的 NO 对 SNGFR 施加向上的压力，并降低 TGF-GTB 系统在正常血容量条件下以环境流速稳定 VLP 的效率。
Nephron filtration rate (SNGFR) and proximal tubular reabsorption are coordinated by the processes of tubuloglomerular feedback (TGF) and glomerulotubular balance (GTB). We examined the role of nitric oxide (NO) in TGF and GTB, by delivering the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) into late proximal nephrons by micropuncture in Inactin-anesthetized euvolemic rats. First, we determined the dependence of SNGFR on late proximal tubular flow rate (VLP) during orthograde microperfusion of Henle's loop downstream from an obstructing wax block (open-loop microperfusion). Second, we examined the homeostatic efficiency of the TGF-GTB system, (i.e., its ability to stabilize VLP) by perturbing VLP in free-flowing nephrons, while using a noninvasive optical technique to measure flow immediately upstream from the perturbation (closed-loop perturbation). Third, we tested whether L-NMMA could alter the afferent signal to TGF by changing the relationship between VLP and the flow rate (VED) or ionic content (CED) of early distal tubular fluid during open-loop microperfusion. During open-loop microperfusion, L-NMMA decreased SNGFR at VLP between 10 and 40 nl/min but did not alter the relationship between VLP and VED or CED. During closed-loop perturbation, L-NMMA did not affect ambient VLP but increased the homeostatic efficiency of the TGF-GTB system. The combined effects on SNGFR and ambient VLP suggest that L-NMMA reduces proximal reabsorption. However, this could account for only a small fraction of the increase in homeostatic efficiency, the greater share of which must be mediated within the juxtaglomerular apparatus. It appears that juxtaglomerular NO exerts an upward pressure on SNGFR and reduces the efficiency of the TGF-GTB system in stabilizing VLP at ambient flow rates under euvolemic conditions.