Eiam-Ong S, Kurtzman N A, Sabatini S
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock.
Kidney Int. 1993 May;43(5):1015-20. doi: 10.1038/ki.1993.143.
Hypokalemic metabolic alkalosis is one of the most common complications of chronic furosemide administration. In this study we examined acid-base composition and ATPase enzyme activities in medullary thick ascending limb of Henle's loop (MTAL) and collecting tubule (CCT and MCT) after seven days of chronic furosemide therapy. All of the studies were conducted in adrenal intact (AI) rats or in adrenalectomized (ADX) glucocorticoid replete rats replaced with a physiological dose of aldosterone (Aldo). Furosemide (F) was administered to each rat by mini-osmotic pump. In the AI+F group, plasma Aldo was high and obvious metabolic alkalosis occurred (HCO3- = 37 +/- 2 mEq/liter vs. 22 +/- 2 mEq/liter in controls, P < 0.005); activities of H-K-ATPase, H-ATPase, and Na-K-ATPase were increased approximately twofold in both CCT and MCT. In the ADX+F group (HCO3- = 28 +/- 2 mEq/liter, P < 0.05 from control), H-ATPase activity was normal in CCT and it was slightly increased in MCT. CCT and MCT H-K-ATPase activities were markedly increased (approximately twofold). Na-K-ATPase activity was the same as control in CCT but it was increased in MCT. In ADX+F+Vanadate (V) group which also had normal Aldo levels, acid-base changes were modest (20 +/- 2 mEq/liter, NS from control); in CCT and MCT H-K-ATPase and Na-K-ATPase activities were markedly reduced, but H-ATPase activity in MCT was increased. In all three experimental groups Na-K-ATPase activity in MTAL was reduced fivefold. Hypokalemia developed in both intact and ADX animals receiving furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)
低钾性代谢性碱中毒是慢性使用呋塞米最常见的并发症之一。在本研究中，我们检测了慢性呋塞米治疗7天后髓袢升支粗段（MTAL）以及集合管（CCT和MCT）的酸碱组成和ATP酶活性。所有研究均在肾上腺完整（AI）大鼠或切除肾上腺（ADX）并用生理剂量醛固酮（Aldo）替代的糖皮质激素充足大鼠中进行。通过微型渗透泵给每只大鼠注射呋塞米（F）。在AI + F组中，血浆醛固酮水平升高，出现明显的代谢性碱中毒（HCO3- = 37 ± 2 mEq/升，而对照组为22 ± 2 mEq/升，P < 0.005）；CCT和MCT中H-K-ATP酶、H-ATP酶和Na-K-ATP酶的活性增加了约两倍。在ADX + F组（HCO3- = 28 ± 2 mEq/升，与对照组相比P < 0.05），CCT中H-ATP酶活性正常，MCT中略有增加。CCT和MCT的H-K-ATP酶活性显著增加（约两倍）。CCT中Na-K-ATP酶活性与对照组相同，但MCT中增加。在醛固酮水平也正常的ADX + F + 钒酸盐（V）组中，酸碱变化较小（20 ± 2 mEq/升，与对照组无显著差异）；CCT和MCT中H-K-ATP酶和Na-K-ATP酶活性显著降低，但MCT中H-ATP酶活性增加。在所有三个实验组中，MTAL中的Na-K-ATP酶活性降低了五倍。接受呋塞米的完整动物和ADX动物均出现低钾血症。（摘要截断于250字）
