Mujais S K, Nascimento L, Rademacher D R, Wilson A, Kurtzman N A
Miner Electrolyte Metab. 1986;12(2):107-12.
Distal acidification was assessed in adrenalectomized (ADX) rats in which the development of acidosis was prevented by oral supplementation with NaHCO3, with or without glucocorticoid replacement. Totally corticosteroid-deficient nonacidotic rats were capable of lowering their urine pH in response to Na2SO4 infusion from a baseline of 7.47 +/- 0.22 to 4.83 +/- 0.1 (p less than 0.001). A similarly intact ability to lower the urine pH was also demonstrated in glucocorticoid-replaced mineralocorticoid-deficient rats. Absolute ammonium excretion was lower in ADX animals compared to controls (0.79 +/- 0.08 vs. 0.46 +/- 0.06 microEq/min, p less than 0.01) but when corrected for the difference in GFR, ammonium excretion was the same in ADX and adrenal-intact rats. During bicarbonate loading and at similar blood and urine pH, and bicarbonate concentrations, the U-B pCO2 gradient was similar in mineralocorticoid-deficient and adrenal intact rats (44 +/- 5.1 vs. 36 +/- 2.6 mm Hg, respectively). Amiloride administration to mineralocorticoid-deficient rats led to a reduction in the U-B pCO2 gradient from 30 +/- 4.5 to 10 +/- 3.0 mm Hg (p less than 0.002). These results indicate that the ability to lower the urine pH and raise the urine pCO2 is intact in the nonacidotic ADX rat; ammonium excretion in this model is reduced in proportion to the observed reduction in GFR, and amiloride administration inhibits acidification in ADX rats. The data strongly suggest the presence of a major site of aldosterone-independent, sodium-dependent acidification mechanism likely located at the level of the cortical collecting tubule.
在肾上腺切除(ADX)大鼠中评估了远端酸化情况,这些大鼠通过口服补充NaHCO₃预防酸中毒的发生,补充时伴有或不伴有糖皮质激素替代。完全缺乏皮质类固醇的非酸中毒大鼠能够响应Na₂SO₄输注将尿液pH从基线的7.47±0.22降低至4.83±0.1(p<0.001)。在补充糖皮质激素的盐皮质激素缺乏大鼠中也证明了类似的降低尿液pH的完整能力。与对照组相比,ADX动物的绝对铵排泄量较低(0.79±0.08对0.46±0.06微当量/分钟)(p<0.01),但校正肾小球滤过率差异后,ADX大鼠和肾上腺完整大鼠的铵排泄量相同。在碳酸氢盐负荷期间,以及在相似的血液和尿液pH及碳酸氢盐浓度下,盐皮质激素缺乏大鼠和肾上腺完整大鼠的尿-血二氧化碳分压梯度相似(分别为44±5.1对36±2.6毫米汞柱)。给盐皮质激素缺乏大鼠施用氨氯吡咪导致尿-血二氧化碳分压梯度从30±4.5降至10±3.0毫米汞柱(p<0.002)。这些结果表明,非酸中毒ADX大鼠降低尿液pH和提高尿液二氧化碳分压的能力是完整的;该模型中的铵排泄量与观察到的肾小球滤过率降低成比例减少,并且施用氨氯吡咪会抑制ADX大鼠的酸化。数据强烈表明存在一个可能位于皮质集合管水平的主要的不依赖醛固酮、依赖钠的酸化机制位点。