Fujimura A, Ebihara A
Department of Clinical Pharmacology, Oita Medical School, Japan.
Life Sci. 1988;42(15):1431-7. doi: 10.1016/0024-3205(88)90053-7.
We have previously demonstrated a time-dependent variability in the diuretic effect of furosemide in rats. The present study was undertaken to evaluate the influence of beta-adrenoceptor blockade on these time-dependent variations. Furosemide (5 mg/kg) was administered intra-arterially in Wistar rats at 1000 hrs (03HALO) or at 2200 hrs (15HALO) with pretreatment with either propranolol (10 mg/kg) or atenolol (10 mg/kg). Urine was collected for 60 min after furosemide administration and urinary excretion of sodium and furosemide were determined respectively. Propranolol pretreatment abolished the temporal variations observed in urine volume, urinary sodium and furosemide levels during the observation periods. With atenolol pretreatment, however, all these variables were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study. These results suggest that the beta-adrenoceptor-mediated stimuli, which is blocked by propranolol but not by atenolol, is responsible for the time-dependent changes in the diuretic effect of furosemide.
我们之前已经证明了呋塞米对大鼠利尿作用存在时间依赖性变化。本研究旨在评估β-肾上腺素能受体阻断对这些时间依赖性变化的影响。在1000时（03HALO）或2200时（15HALO）给Wistar大鼠动脉内注射呋塞米（5mg/kg），并预先用普萘洛尔（10mg/kg）或阿替洛尔（10mg/kg）进行预处理。呋塞米给药后收集60分钟尿液，分别测定尿钠和呋塞米的排泄量。普萘洛尔预处理消除了观察期间尿量、尿钠和呋塞米水平的时间变化。然而，与之前的研究一样，阿替洛尔预处理后，所有这些变量在1000时（03HALO）显著高于2200时（15HALO）。这些结果表明，普萘洛尔可阻断但阿替洛尔不能阻断的β-肾上腺素能受体介导的刺激，是呋塞米利尿作用时间依赖性变化的原因。
