Levin D L, Chou S Y, Ferder L F, Liebman P H, Porush J G
J Lab Clin Med. 1976 May;87(5):804-12.
In an attempt to examine the effects of mild and severe chronic metabolic acidosis on proximal tubule sodium reabsorption, 6 dogs were given 10 mEq. per kilogram per day and 5 dogs were given 20mEq. per kilogram per day of ammonium chloride for 3 days and compared to 12 normal dogs during a steady-state water diuresis and following the administration of ethacrynic acid (EA) intravenously (2 mg. per kilogram) utilizing standard clearance methodology, In the severely acidotic group (pH decrease is greater tthan 0.2) plasma pH was 7.08 +/- 0.06 and plasma bicarbonate was 6.3 +/- 1.0 Eq. per liter compared to a pH of 7.33 +/-0.02 and bicarbonate of 13.4 +/- 0.7 in mild acidosis (pH decrease is less than 0.2). During a steady-state water diuresis urine flow was 14.2 +/- 0.9 in severely acidotic compared to 10.5 +/-0.7 ml. per minute per 100 ml. glomerular filtration rate (GFR) in normal dogs (p is less than 0.01). Following EA sodium clearance increased 38.4 +/- 3.5 in severely acidotic dogs and 27.6 +/- 2.0 ml. per minute per 100 ml. GFR in normal dogs (p is less than 0.02). In mild acidosis, steady-state fractional urine flow and the increase in fractional sodium clearance following EA were not significantly different than normal dogs. We conclude that chronic metabolic acidosis leads to an increase in distal solute load and enhanced natriuretic effect of EA secondary to a decrease in proximal tubule sodium reabsorption which may be dependent upon the degree of reduction in the plasma bicarbonate level.
为了研究轻度和重度慢性代谢性酸中毒对近端肾小管钠重吸收的影响，给6只狗每天每千克体重给予10毫当量氯化铵，给5只狗每天每千克体重给予20毫当量氯化铵，持续3天，并在稳态水利尿期间以及静脉注射依他尼酸（EA，每千克体重2毫克）后，利用标准清除率方法将它们与12只正常狗进行比较。在重度酸中毒组（pH下降大于0.2），血浆pH为7.08±0.06，血浆碳酸氢盐为6.3±1.0当量/升，而轻度酸中毒组（pH下降小于0.2）的pH为7.33±0.02，碳酸氢盐为13.4±0.7。在稳态水利尿期间，重度酸中毒狗的尿流率为14.2±0.9，而正常狗为每分钟每100毫升肾小球滤过率（GFR）10.5±0.7毫升（p<0.01）。注射EA后，重度酸中毒狗的钠清除率增加了38.4±3.5，而正常狗为每分钟每100毫升GFR增加27.6±2.0毫升（p<0.02）。在轻度酸中毒时，稳态尿流分数以及注射EA后钠清除分数的增加与正常狗无显著差异。我们得出结论，慢性代谢性酸中毒导致远端溶质负荷增加，并增强了EA的利钠作用，这继发于近端肾小管钠重吸收减少，这可能取决于血浆碳酸氢盐水平降低的程度。
