Schnermann J, Ploth D W, Hermle M
Pflugers Arch. 1976 Apr 6;362(3):229-40. doi: 10.1007/BF00581175.
To define the luminal agent(s) responsible for the reduction of nephron filtration rate following increases of loop of Henle flow rate early proximal flow rate (EPFR) during loop perfusion with 17 different salt solutions were compared to the non-perfused tubules. During orthograde microperfusions a reduction of EPFR as indication of a feedback response was noted with a number of monovalent Cl- and Br- salts (LiCl, KCl, NaCl, RbCl, CsCl, NH4Cl, choline Cl, NaBr, KBr), with Na+ salts except Na acetate (NaHCO3, NaNO3, NaF, NaI, NaSCN), and with CaCl2 and MgCl2. These latter 2 solutions where used in a concentration of 70 mM while all other solutions had a concentration of 140 mM. During retrograde perfusion from the distal to the proximal end of the loop of Henle EPFR fell significantly with Cl- and Br- salts with percentage changes of EPFR ranging from -8.0 to -44.3%. In contrast, Cl- free salts and Cl- salts of divalent cations were associated with percentage changes of EPFR ranging from +7.1 to -6.2%, significance being reached only during perfusion with NaSCN. When furosemide (5 x 10(-4) M) was added to NaBr or KBr a feedback response was not observed. During orthograde perfusion with NaNO3 distal Cl- concentrations were 44.2 +/- 5.08, mM (mean +/- S.E.) at a perfusion rate of 10 nl/min and 59.1 +/- 3.93 mM at a rate of 40 nl/min. CaCl2 perfusion induced a marked elevation of distal Cl- concentrations to levels higher than 140 mM. Loop chloride handling was normal during RbCl perfusion. The magnitude of the feedback response during retrograde perfusion was not changed by lowering NaCl concentration from 140 to 60 mM, but fell when NaCl concentration was further reduced. In contrast to orthograde perfusions it was insensitive to changes in flow rate. Our results are compatible with the thesis that feedback responses depend critically upon the rate of Cl- transport probably across the macula densa cells. Br- ions can replace Cl- because they appear to share a common transport pathway which can be inhibited with furosemide. Unspecificity of feedback responses during orthograde microperfusions is due to presence of Cl- ions in the macula densa region even when solutions are initially Cl- free. Cl- salts of divalent cations do not elicit a feedback response because Cl- transport is severely curtailed.
为了确定在髓袢灌注期间，随着髓袢升支粗段流速和早期近端流速（EPFR）增加而导致肾单位滤过率降低的管腔介质，将17种不同盐溶液灌注时的情况与未灌注的肾小管进行了比较。在顺行微灌注过程中，发现多种单价Cl⁻和Br⁻盐（LiCl、KCl、NaCl、RbCl、CsCl、NH₄Cl、胆碱Cl、NaBr、KBr）、除醋酸钠外的Na⁺盐（NaHCO₃、NaNO₃、NaF、NaI、NaSCN）以及CaCl₂和MgCl₂会引起EPFR降低，这表明存在反馈反应。后两种溶液的浓度为70 mM，而所有其他溶液的浓度为140 mM。在从髓袢远端向近端逆行灌注过程中，Cl⁻和Br⁻盐会使EPFR显著下降，EPFR的百分比变化范围为 -8.0%至 -44.3%。相比之下，无Cl⁻盐和二价阳离子的Cl⁻盐使EPFR的百分比变化范围为 +7.1%至 -6.2%，仅在灌注NaSCN时达到显著水平。当向NaBr或KBr中加入呋塞米（5×10⁻⁴ M）时，未观察到反馈反应。在以10 nl/min的灌注速率顺行灌注NaNO₃时，远端Cl⁻浓度为44.2±5.08 mM（平均值±标准误），以40 nl/min的速率灌注时为59.1±3.93 mM。CaCl₂灌注会使远端Cl⁻浓度显著升高至高于140 mM的水平。在RbCl灌注期间，髓袢对氯离子的处理正常。将NaCl浓度从140 mM降至60 mM时，逆行灌注期间反馈反应的幅度不变，但当NaCl浓度进一步降低时，反馈反应幅度下降。与顺行灌注不同，它对流速变化不敏感。我们的结果与以下观点一致，即反馈反应关键取决于可能跨致密斑细胞的Cl⁻转运速率。Br⁻离子可以替代Cl⁻，因为它们似乎共享一条可被呋塞米抑制的共同转运途径。顺行微灌注期间反馈反应的非特异性是由于即使溶液最初无Cl⁻，致密斑区域仍存在Cl⁻离子。二价阳离子的Cl⁻盐不会引发反馈反应，因为Cl⁻转运受到严重限制。
