Fujimura A, Sudoh T, Ebihara A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Life Sci. 1994;55(5):373-8. doi: 10.1016/0024-3205(94)00648-2.
We have recently demonstrated that the time-dependent difference in urinary excretion of furosemide, a loop diuretic, diminishes during the aging process and disappears by 18 months of age in rats. The present study was undertaken to examine whether the amplitude of the daily variations in the urinary excretion of furosemide or their pattern, or both, are influenced in aged animals. Young (3 months of age) and aged (30 months of age) Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Furosemide (30 mg/kg) was given orally at 4 am, 8 am, 12 am, 4 pm, 8 pm or 12 pm. Urine was collected for 8 hours after furosemide administration and urinary excretion of furosemide was determined. There were significant daily variations in the urinary furosemide and the urine volume with the peak at 8 am and the trough at 12 pm in both groups of rats. The differences in these parameters between the 8 am and 12 pm trials were significantly smaller in the aged than in the young rats. These results suggest that the age-related alteration in the time-dependent phenomenon of furosemide is caused by the decreased amplitude of the daily variation in the urinary furosemide excretion and its diuretic effect.
我们最近证明，在衰老过程中，袢利尿剂呋塞米的尿排泄量随时间的差异会减小，并在大鼠18月龄时消失。本研究旨在探讨老年动物中呋塞米尿排泄量的每日变化幅度或其模式，或两者是否受到影响。将年轻（3月龄）和老年（30月龄）的Wistar大鼠饲养在上午7点至下午7点光照、下午7点至上午7点黑暗的条件下。在凌晨4点、上午8点、中午12点、下午4点、晚上8点或晚上12点口服给予呋塞米（30mg/kg）。给药后收集8小时尿液，并测定呋塞米的尿排泄量。两组大鼠的尿呋塞米和尿量均有显著的每日变化，上午8点达到峰值，中午12点达到谷值。老年大鼠上午8点和中午12点试验之间这些参数的差异明显小于年轻大鼠。这些结果表明，呋塞米时间依赖性现象的年龄相关改变是由尿呋塞米排泄量及其利尿作用的每日变化幅度减小引起的。
