Differential effects of acute mineralo- and glucocorticosteroid administration on renal acid elimination.
Differential effects of acute mineralo- and glucocorticosteroid administration on renal acid elimination.
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急性矿物皮质类固醇和糖皮质激素给药对肾酸消除的不同影响。
DOI：
10.1038/ki.1982.61
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发表时间：
1982
影响因子：
19.6
通讯作者：
Giebisch,G
中科院分区：
文献类型：
--
作者：
Wilcox,CS;Cemerikic,DA;Giebisch,G
方法选择术后3 ~ 6d的ADX大鼠作为研究激素给药对排酸作用的模型，此时基础水平的皮质类固醇激素对排酸作用无影响。通过给予酸（氯化铵）和缓冲液（中性磷酸钠）刺激酸消除。急性给予类固醇是为了最大限度地减少对肾脏的次要影响，例如由液体和电解质平衡改变或代谢影响引起的影响。需要大量的实验来获得矿物质和糖皮质酮的完整剂量反应关系，以评估这些激素作用的特异性。此外，为了检查是否可能需要一类类固醇才能完全表达另一类类固醇的作用，在存在固定剂量的另一类类固醇的情况下，重新定义了每种类固醇的剂量-反应关系。重复先前的研究（6，11，28），在初步实验中发现醛甾酮在6小时内发挥其最大的肾脏作用，并在尿液收集前2小时给予。地塞米松的作用需要较长的时间才能显现（7，11，29）;在收集尿液前15和2小时给予两次，我们选择研究清醒的、无创伤的动物，通过麻醉和急性手术干预来减少对这些脆弱动物的进一步压力，否则这些压力可能会控制它们的肾脏功能。包括假手术大鼠（SHAM），因此我们可以观察具有完整肾上腺的大鼠中的肾脏酸消除。然而，肾上腺切除术对肾和心血管功能以及液体和电解质平衡有预先发现的影响，液体和电解质平衡也会影响肾脏的酸排泄。虽然调节饮食摄入量以尽量减少ADX和SHAM组之间的差异，但这些变量并不完全匹配;因此，SHAM和ADX大鼠之间的任何差异不仅反映了类固醇作用消除对肾脏的影响，而且还反映了肾上腺功能不全本身的更广泛影响。我们的研究主要侧重于比较肾脏酸排泄
Methods The model chosen to investigate the effects of hormone administration on acid elimination was the ADX rat studied 3 to 6 days after operation when results could not be influenced by basal levels of corticosteroids. Acid elimination was stimulated by the administration of acid (ammonium chloride) and buffer (neutral sodium phosphate). Steroids were given acutely to minimize secondary effects on the kidney caused, for example, by altered fluid and electrolyte balances or metabolic effects. Large numbers of experiments were required to obtain full dose-response relationships for mineralo-and glucocorticoster-oids to assess the specificity of the actions of these hormones. In addition, to examine whether a steroid of one class might be required to permit full expression of the effects of a steroid of the other class, the dose-response relationships for each steroid were redefined in the presence of a fixed dose of the steroid of the other class. Confirming previous studies (6, 11, 28), aldos-terone was found in preliminary experiments to exert its maximal renal actions within 6 hr and was given 2 hr before urine collection. The effects of dexamethasone required a longer time to develop (7, 11, 29); it was given twice, 15 and 2 hr before urine collection.We elected to study conscious, nontraumatized animals to reduce further stress on these fragile animals by anesthesia and acute surgical intervention which might otherwise have dominated their renal performance. Sham-operated rats (SHAM) were included so we could observe renal acid elimination in rats with intact adrenal glands. However, adrenalectomy has pro-found effects on renal and cardiovascular function, as well as on fluid and electrolyte balance which also affects renal acid excretion. Although dietary intakes were regulated to minimize differences between the ADX and SHAM groups, these variables were not perfectly matched; consequently, any differences between SHAM and ADX rats reflect not only the effects of the elimination of steroid action on the kidney but also the more widespread effects of adrenal insufficiency, per se. Our study's main emphasis rests on comparisons of renal acid excretion