Stanton B, Giebisch G, Klein-Robbenhaar G, Wade J, DeFronzo R A
J Clin Invest. 1985 Apr;75(4):1317-26. doi: 10.1172/JCI111832.
Clearance experiments were carried out in pair-fed rats to examine the long-term effects of adrenalectomy and selective adrenal corticosteroid replacement in physiological amounts on renal potassium transport. To this end, clearance studies were conducted in rats that were sham operated, or adrenalectomized (ADX). ADX animals were given either vehicle, aldosterone (0.5 microgram/100 g body wt per day), dexamethasone (1.2 micrograms/100 g body wt per day), or aldosterone and dexamethasone, by osmotic minipump for 7-9 d whereupon clearance experiments were conducted. After chronic hormone treatment, during basal conditions when only Ringers solution was infused, all groups excreted similar amounts of potassium. However, in all ADX animals without mineralocorticoid replacement, the maintenance of urinary potassium excretion at control levels was associated with hyperkalemia, increased urine flow, and natriuresis; all are factors known to stimulate urinary potassium excretion. During acute potassium infusion, the increase in urinary potassium excretion was less in ADX rats than in controls. This functional deficiency in potassium excretion was partially corrected by dexamethasone and was uniformly associated with a significant increase in urine flow. Aldosterone replacement or aldosterone and dexamethasone given together chronically, sharply increased potassium excretion but did not restore excretion to control levels. Only acute aldosterone infusion (0.2 microgram/100 g body wt bolus plus 0.2 microgram/100 g body wt per hour), superimposed upon chronic aldosterone and dexamethasone treatment, fully restored potassium excretion to control levels. This aldosterone induced enhancement of potassium excretion, both chronic and acute, was not associated with hyperkalemia, and increased urine flow or natriuresis. Thus, physiological levels of both classes of adrenal corticosteroids stimulate renal potassium excretion albeit by different mechanisms. Mineralocorticoids stimulate tubular potassium excretion directly, whereas glucocorticoids augment excretion indirectly by increasing fluid and sodium delivery along the distal nephron.
在成对喂养的大鼠中进行清除实验，以研究肾上腺切除术和生理剂量的选择性肾上腺皮质激素替代对肾钾转运的长期影响。为此，在假手术或肾上腺切除（ADX）的大鼠中进行清除研究。通过渗透微型泵给ADX动物注射溶剂、醛固酮（每天0.5微克/100克体重）、地塞米松（每天1.2微克/100克体重）或醛固酮和地塞米松，持续7 - 9天，然后进行清除实验。慢性激素治疗后，在仅输注林格氏液的基础条件下，所有组排泄的钾量相似。然而，在所有未用盐皮质激素替代的ADX动物中，尿钾排泄维持在对照水平与高钾血症、尿流量增加和利钠有关；所有这些都是已知刺激尿钾排泄的因素。在急性钾输注期间，ADX大鼠尿钾排泄的增加低于对照组。这种钾排泄的功能缺陷部分被地塞米松纠正，并且一致地与尿流量的显著增加有关。长期给予醛固酮替代或醛固酮与地塞米松联合使用，显著增加了钾排泄，但未将排泄恢复到对照水平。仅在慢性醛固酮和地塞米松治疗基础上叠加急性醛固酮输注（0.2微克/100克体重推注加0.2微克/100克体重每小时），才能将钾排泄完全恢复到对照水平。这种醛固酮诱导的慢性和急性钾排泄增强与高钾血症、尿流量增加或利钠无关。因此，两类肾上腺皮质激素的生理水平均刺激肾钾排泄，尽管机制不同。盐皮质激素直接刺激肾小管钾排泄，而糖皮质激素通过增加远端肾单位的液体和钠输送间接增加排泄。
