Eiam-Ong S, Dafnis E, Spohn M, Kurtzman N A, Sabatini S
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430.
Am J Physiol. 1993 Dec;265(6 Pt 2):F875-80. doi: 10.1152/ajprenal.1993.265.6.F875.
In previous studies we suggested that urinary tract obstruction and chronic administration of lithium or amiloride were models of "voltage-dependent" distal renal tubular acidosis (DRTA). Subsequently, differences among these three models suggested that the pathogenesis was far more complex than we originally proposed. A recent study showed that H-adenosinetriphosphatase (H-ATPase) activity was decreased in all three experimental models. In the current experiments we examined the effect of 24-h unilateral ureteral obstruction (UUO) and chronic administration of amiloride and lithium on collecting tubule H-K-ATPase, the other renal H-ATPase enzyme. In the obstructed kidney, cortical collecting tubule (CCT) H-K-ATPase activity was enhanced by 73 +/- 10.0%, whereas the enzyme activity in medullary collecting tubule (MCT) was decreased by 67 +/- 5.4%. In the normal contralateral kidney, activities of H-ATPase, H-K-ATPase, and Na-K-ATPase were increased by approximately 30% in both CCT and MCT. Following amiloride (3 mg.kg-1.day-1 x 3 days ip), rats had normal acid-base status, slight hyperkalemia, and markedly elevated plasma aldosterone levels. Both CCT and MCT H-K-ATPase activities in amiloride-treated rats were unchanged. After LiCl (4 meq.kg-1.day-1 x 3 days ip), rats developed mild metabolic acidosis and had normokalemia and normal aldosterone status. CCT H-K-ATPase activity in lithium-treated rats was decreased by 64 +/- 8.8%, whereas the enzyme activity in MCT remained unchanged. Lithium in vitro (30 meq/l) inhibited CCT, but not MCT, H-K-ATPase activity, whereas amiloride had no effect on the enzyme activity. (ABSTRACT TRUNCATED AT 250 WORDS)
在先前的研究中，我们提出尿路梗阻以及长期给予锂盐或氨氯吡咪是“电压依赖性”远端肾小管性酸中毒（DRTA）的模型。随后，这三种模型之间的差异表明其发病机制远比我们最初提出的要复杂得多。最近一项研究显示，在所有这三种实验模型中，氢 - 三磷酸腺苷酶（H - ATPase）活性均降低。在当前实验中，我们检测了24小时单侧输尿管梗阻（UUO）以及长期给予氨氯吡咪和锂盐对集合管氢 - 钾 - 三磷酸腺苷酶（H - K - ATPase）（另一种肾脏H - ATPase酶）的影响。在梗阻侧肾脏，皮质集合管（CCT）的H - K - ATPase活性增强了73±10.0%，而髓质集合管（MCT）中的酶活性降低了67±5.4%。在正常的对侧肾脏中，CCT和MCT中H - ATPase、H - K - ATPase以及钠 - 钾 - 三磷酸腺苷酶（Na - K - ATPase）的活性均增加了约30%。给予氨氯吡咪（3毫克·千克⁻¹·天⁻¹×3天，腹腔注射）后，大鼠酸碱状态正常，有轻微高钾血症，血浆醛固酮水平显著升高。氨氯吡咪处理的大鼠CCT和MCT的H - K - ATPase活性均未改变。给予氯化锂（4毫当量·千克⁻¹·天⁻¹×3天，腹腔注射）后，大鼠出现轻度代谢性酸中毒，血钾正常，醛固酮状态正常。锂处理的大鼠CCT的H - K - ATPase活性降低了64±8.8%，而MCT中的酶活性保持不变。体外锂（30毫当量/升）抑制CCT而非MCT的H - K - ATPase活性，而氨氯吡咪对该酶活性无影响。（摘要截选至250词）
