Div. of Nephrology-Hypertension, VASDHS, 3350 La Jolla Village Dr. 9151, San Diego, CA 92161.
Am J Physiol Renal Physiol. 2014 Jan;306(2):F172-80. doi: 10.1152/ajprenal.00431.2013. Epub 2013 Nov 20.
We previously reported internephron heterogeneity in the tubuloglomerular feedback (TGF) response 1 wk after subtotal nephrectomy (STN), with 50% of STN nephrons exhibiting anomalous TGF (Singh P, Deng A, Blantz RC, Thomson SC. Am J Physiol Renal Physiol 296: F1158-F1165, 2009). Presently, we tested the theory that anomalous TGF is an adaptation of the STN kidney to facilitate increased distal delivery when NaCl balance forces the per-nephron NaCl excretion to high levels. To this end, the effect of dietary NaCl on the TGF response was tested by micropuncture in STN and sham-operated Wistar rats. An NaCl-deficient (LS) or high-salt NaCl diet (HS; 1% NaCl in drinking water) was started on day 0 after STN or sham surgery. Micropuncture followed 8 days later with measurements of single-nephron GFR (SNGFR), proximal reabsorption, and tubular stop-flow pressure (PSF) obtained at both extremes of TGF activation, while TGF was manipulated by microperfusing Henle's loop (LOH) from the late proximal tubule. Activating TGF caused SNGFR to decline by similar amounts in Sham-LS, Sham-HS and STN-LS [ΔSNGFR (nl/min) = -16 ± 2, -11 ± 3, -11 ± 2; P = not significant by Tukey]. Activating TGF in STN-HS actually increased SNGFR by 5 ± 2 nl/min (P < 0.0005 vs. each other group by Tukey). HS had no effect on the PSF response to LOH perfusion in sham [ΔPSF (mmHg) = -9.6 ± 1.1 vs. -9.8 ± 1.0] but eliminated the PSF response in STN (+0.3 ± 0.9 vs. -5.7 ± 1.0, P = 0.0002). An HS diet leads to anomalous TGF in the early remnant kidney, which facilitates NaCl and fluid delivery to the distal nephron.
我们之前报道过,在部分肾切除术后 1 周,肾小管肾小球反馈(TGF)反应存在肾单位间的异质性,50%的部分肾切除肾单位表现出异常的 TGF(Singh P、Deng A、Blantz RC、Thomson SC. Am J Physiol Renal Physiol 296: F1158-F1165, 2009)。目前,我们验证了这一理论,即异常的 TGF 是部分肾切除肾脏的一种适应机制,可在 NaCl 平衡迫使每个肾单位的 NaCl 排泄达到高水平时,促进远端输送的增加。为此,通过微穿刺法在部分肾切除和假手术的 Wistar 大鼠中测试了饮食 NaCl 对 TGF 反应的影响。在部分肾切除或假手术后的第 0 天开始给予低钠(LS)或高盐 NaCl 饮食(HS;饮用水中 1%NaCl)。8 天后进行微穿刺,测量 TGF 激活的两个极端时的单个肾单位肾小球滤过率(SNGFR)、近端重吸收和管状停流压(PSF),同时通过从近端小管晚期微灌流 Henle 袢(LOH)来调节 TGF。激活 TGF 可使 Sham-LS、Sham-HS 和 STN-LS 的 SNGFR 以相似的幅度下降[ΔSNGFR(nl/min)=-16±2、-11±3、-11±2;Tukey 检验无统计学差异]。在 STN-HS 中激活 TGF 实际上使 SNGFR 增加了 5±2 nl/min(Tukey 检验与其他组相比 P<0.0005)。HS 对 Sham 中 LOH 灌注的 PSF 反应没有影响[ΔPSF(mmHg)=-9.6±1.1 与-9.8±1.0],但消除了 STN 中的 PSF 反应(+0.3±0.9 与-5.7±1.0,P=0.0002)。HS 饮食导致早期残肾中出现异常的 TGF,从而促进 NaCl 和液体输送到远端肾单位。