van Buren M, Boer P, Koomans H A
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
J Clin Endocrinol Metab. 1993 Oct;77(4):902-9. doi: 10.1210/jcem.77.4.8408463.
To examine the role of mineralocorticoid and glucocorticoid in potassium (K) tolerance in healthy humans, we studied the effects of canrenoate, a mineralocorticoid antagonist, and RU486, a glucocorticoid antagonist, on the excretion of a KCl load. Canrenoate (200 mg, iv) or RU486 (400 mg, orally) was administered 150 min before a KCl load (1 mmol/kg BW, orally) in seven healthy males undergoing maximal water diuresis. Clearance studies were extended for 5 h after the KCl load, and the data were compared with time control, KCl load alone, and canrenoate alone. KCl increased K excretion (from 18.8 +/- 2.4 to 63.3 +/- 3.9 mmol/5 h; P < 0.01) and sodium (Na) excretion (from 35.9 +/- 2.1 to 72.9 +/- 6.0 mmol/5 h; P < 0.01). Clearance calculations, based on maximal water diuresis, were compatible with increased distal Na and volume delivery. Canrenoate alone modestly increased basal cumulative NaCl excretion and had no effect on K excretion. However, canrenoate blunted the kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compared to KCl alone) and stimulated natriuresis in a complementary way. Clearance data were compatible with diminished distal Na reabsorption and K secretion in response to an undisturbed KCl-induced increase in distal Na delivery. RU486 did not influence the excretion of the KCl load or its effects on renal sodium handling parameters, although effective glucocorticoid receptor blockade was likely to be present in view of the increase in plasma cortisol. These data suggest that in healthy humans, mineralocorticoid activity, but not glucocorticoid activity, is involved in the elimination of a K load. The latter contrasts with data in adrenalectomized animals, in which situation glucocorticoid as well as aldosterone are indispensible for normal K tolerance.
为研究盐皮质激素和糖皮质激素在健康人体钾（K）耐受性中的作用，我们研究了盐皮质激素拮抗剂坎利酸钾和糖皮质激素拮抗剂RU486对氯化钾负荷排泄的影响。在7名接受最大水利尿的健康男性口服氯化钾负荷（1 mmol/kg体重）前150分钟，静脉注射坎利酸钾（200 mg）或口服RU486（400 mg）。氯化钾负荷后进行5小时的清除率研究，并将数据与时间对照、单独氯化钾负荷以及单独坎利酸钾进行比较。氯化钾增加了钾排泄（从18.8±2.4增至63.3±3.9 mmol/5小时；P<0.01）和钠（Na）排泄（从35.9±2.1增至72.9±6.0 mmol/5小时；P<0.01）。基于最大水利尿的清除率计算结果与远曲小管钠和容量输送增加一致。单独使用坎利酸钾适度增加了基础累积氯化钠排泄，但对钾排泄无影响。然而，坎利酸钾减弱了氯化钾负荷后的尿钾排泄（51.9±4.4 mmol/5小时；与单独使用氯化钾相比，P<0.05），并以互补方式刺激了尿钠排泄。清除率数据与远曲小管钠重吸收减少和钾分泌减少一致，这是对未受干扰的氯化钾诱导的远曲小管钠输送增加的反应。尽管鉴于血浆皮质醇增加可能存在有效的糖皮质激素受体阻断，但RU486不影响氯化钾负荷的排泄或其对肾钠处理参数的影响。这些数据表明，在健康人体中，参与钾负荷清除的是盐皮质激素活性而非糖皮质激素活性。这与肾上腺切除动物的数据形成对比，在那种情况下，糖皮质激素以及醛固酮对于正常的钾耐受性都是不可或缺的。
