Galla J H, Bonduris D N, Sanders P W, Luke R G
J Clin Invest. 1984 Dec;74(6):2002-8. doi: 10.1172/JCI111622.
We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and 125I-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25 +/- 1 to 43 +/- 1 meq/L; P less than 0.01), distally determined SNGFR declined progressively (40.9 +/- 1.7 to 28.3 +/- 1.8 nl/min; P less than 0.01), while in early distal tubule fluid, flow rate (8.6 +/- 0.7 to 3.4 +/- 0.6 nl/min) and Cl concentration (36 +/- 2 to 19 +/- 3 meq/L) decreased and osmolality (110 +/- 5 to 208 +/- 12 mosmol/kg) increased (P less than 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009 +/- 112 to 765 +/- 128 peq/min; P less than 0.01). In early distal tubule fluid, Cl concentration correlated positively and osmolality negatively with distally determined SNGFR (P less than 0.05). Proximally determined SNGFRs did not differ among the four groups. Proximal tubule stop-flow pressure responses to increasing rates of orthograde perfusion of the loop segment from 0 to 40 nl/min did not differ between groups CON and CDA-2. We interpret these data to show that reductions in SNGFR in CDA in the rat can occur by tubuloglomerular feedback (TGF) in the absence of differences in ECF volume or of alterations in TGF sensitivity during metabolic alkalosis. Of the proposed signals for TGF sensed by the macula densa, distal tubule fluid osmolality or some related variable is the signal most compatible with our data.
我们最近描述了在无容量耗竭的氯耗竭性碱中毒（CDA）中浅表肾单位肾小球滤过率（SNGFR）降低的情况。为阐明这一现象的机制，我们研究了通过对0.15M NaHCO₃进行一或两次腹膜透析以及向Sprague-Dawley大鼠输注不同Cl⁻和HCO₃⁻含量的电解质所产生的CDA严重程度逐渐增加的三个阶段（CDA-1、2和3组）；对照大鼠（CON）接受针对林格氏-HCO₃的透析和输注。通过血压、血细胞比容、血浆蛋白浓度和¹²⁵I-白蛋白空间评估细胞外液（ECF）容量；这四个组中的这些变量均无差异。对最末端近端和最早远端曲部进行微穿刺。随着CDA从CON组强化至CDA-3组（血浆总CO₂从25±1升至43±1mEq/L；P＜0.01），远端测定的SNGFR逐渐下降（从40.9±1.7降至28.3±1.8nl/min；P＜0.01），而在早期远端小管液中，流速（从8.6±0.7降至3.4±0.6nl/min）和Cl⁻浓度（从36±2降至19±3mEq/L）降低，渗透压（从110±5升至208±12mosmol/kg）升高（P＜0.01），并且在髓袢节段，Cl⁻重吸收逐渐减少（从2009±112降至765±128peq/min；P＜0.01）。在早期远端小管液中，Cl⁻浓度与远端测定的SNGFR呈正相关，渗透压与远端测定的SNGFR呈负相关（P＜0.05）。近端测定的SNGFR在这四个组中无差异。CON组和CDA-2组之间，近端小管对髓袢节段从0至40nl/min的正向灌注速率增加的停流压力反应无差异。我们对这些数据的解释是，在大鼠CDA中，SNGFR的降低可通过管球反馈（TGF）发生，而此时细胞外液容量无差异，且在代谢性碱中毒期间TGF敏感性无改变。在致密斑所感知的TGF的假定信号中，远端小管液渗透压或某些相关变量是与我们的数据最相符的信号。
