Hulter H N, Sebastian A, Sigala J F, Licht J H, Glynn R D, Schambelan M, Biglieri E G
Am J Physiol. 1980 Feb;238(2):F79-91. doi: 10.1152/ajprenal.1980.238.2.F79.
In dogs dietary K+ restriction (16 days) results in diminished urinary net acid excretion (NAE) and systemic hyperchloremic metabolic acidosis (sigma delta NAE, -200 meq; delta[HCO3-]p, -2.9 +/- 0.3 meq/liter, P less than 0.05). Urinary aldosterone (aldo) excretion decreased by 34 +/- 3% (P less than 0.001) and metabolic clearance rate of aldo increased by 80 +/- 17% (P less than 0.02) during K+ restriction. Daily subcutaneous injection of a small amount of exogenous aldo (20 micrograms) during K+ restriction significantly attenuated the reduction in NAE (sigma delta NAE -51 vs. -200 meq, P less than 0.05) without raising plasma aldo concentrations to levels greater than control. These findings suggest that hypoaldosteronism induced by potassium depletion is at least in part the cause of the observed renal tubular acidosis. In adrenalectomized (ADX) dogs maintained on fixed mineralocorticoid and glucocorticoid replacement (aldo dose 60 micrograms/day), K+ restriction resulted in a significant degree of renal metabolic acidosis (delta[HCO3-]p, -1.4 +/- 0.3 meq/liter, P less than 0.01). In these ADX dogs, the exogenous supply of aldo was fixed but hypoaldosteronism may have developed owing to increased metabolic clearance rate of aldo caused by dietary K+ depletion. When mineralocorticoid replacement was withheld in ADX dogs, the steady-state degree of renal metabolic acidosis was no more severe in animals with preexisting dietary K+ depletion (16 days) than in the same animals when mineralocorticoid was withheld without preexisting K+ depletion. Thus, when neither endogenous nor exogenous aldo is present, K+ depletion does not result in a renal acidosis-producing effect that exacerbates that of aldo deficiency. The results of these studies suggest that the reduction in NAE and consequent metabolic acidosis induced by dietary K+ depletion is at least in part a consequence of aldo deficiency, and provide no evidence of an additional defect in acidification not caused by aldo deficiency.
在犬类中，饮食钾限制（16天）会导致尿净酸排泄（NAE）减少和全身性高氯性代谢性酸中毒（σΔNAE，-200 毫当量；Δ[HCO3-]p，-2.9±0.3 毫当量/升，P<0.05）。钾限制期间，尿醛固酮（aldo）排泄减少了 34±3%（P<0.001），而醛固酮的代谢清除率增加了 80±17%（P<0.02）。在钾限制期间，每天皮下注射少量外源性醛固酮（20 微克）可显著减轻 NAE 的降低（σΔNAE -51 对 -200 毫当量，P<0.05），且不会使血浆醛固酮浓度升高至高于对照组的水平。这些发现表明，钾缺乏诱导的醛固酮减少至少部分是观察到的肾小管酸中毒的原因。在维持固定盐皮质激素和糖皮质激素替代治疗（醛固酮剂量 60 微克/天）的肾上腺切除（ADX）犬中，钾限制导致了显著程度的肾性代谢性酸中毒（Δ[HCO3-]p，-1.4±0.3 毫当量/升，P<0.01）。在这些 ADX 犬中，醛固酮的外源性供应是固定的，但由于饮食钾缺乏导致醛固酮的代谢清除率增加，可能发生了醛固酮减少。当在 ADX 犬中停止盐皮质激素替代治疗时，预先存在饮食钾缺乏（16 天）的动物的肾性代谢性酸中毒稳态程度并不比未预先存在钾缺乏而停止盐皮质激素治疗的同一动物更严重。因此，当既无内源性也无外源性醛固酮时，钾缺乏不会导致产生加剧醛固酮缺乏所致肾性酸中毒的效应。这些研究结果表明，饮食钾缺乏诱导的 NAE 降低及随之而来的代谢性酸中毒至少部分是醛固酮缺乏的结果，且没有证据表明存在不由醛固酮缺乏引起的额外酸化缺陷。
