Kikkoji T, Kamiya A, Inui K, Hori R
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Pharm Res. 1988 Nov;5(11):699-703. doi: 10.1023/a:1015951710204.
A urinary excretion-response curve representing the urinary excretion rate of furosemide versus the urinary excretion rate of (Na+ + K+) was used to analyze furosemide action in rats with uranyl nitrate-induced acute renal failure (ARF) with and without dopamine coadministration. Urinary excretion of furosemide, but not its serum concentration, was the determinant for the diuretic action of furosemide. Increased diuretic response was observed in ARF rats, although the total diuretic response and urinary recovery of furosemide within 2 hr decreased. Dopamine enhanced furosemide-induced diuresis in ARF rats in terms of the total urine output and urinary electrolyte excretion, although the urinary excretion-response curves were not different. This enhancement by dopamine was found to be caused by the augmented urinary excretion of furosemide and the increased response to this drug in ARF rats. These findings suggest the contribution of decreased concentrating ability along the nephron and/or increased sensitivity of cells at the site of action to this drug.
使用一条表示呋塞米尿排泄率与（Na⁺ + K⁺）尿排泄率关系的尿排泄-反应曲线，来分析在有或无多巴胺共同给药情况下，硝酸铀酰诱导的大鼠急性肾衰竭（ARF）中呋塞米的作用。呋塞米的利尿作用决定因素是其尿排泄量，而非血清浓度。尽管2小时内呋塞米的总利尿反应和尿回收率降低，但ARF大鼠的利尿反应仍增强。就总尿量和尿电解质排泄而言，多巴胺增强了ARF大鼠中呋塞米诱导的利尿作用，尽管尿排泄-反应曲线并无差异。发现多巴胺的这种增强作用是由于ARF大鼠中呋塞米尿排泄增加以及对该药物的反应增强所致。这些发现提示，沿肾单位浓缩能力降低和/或作用部位细胞对该药物的敏感性增加起了作用。
