Shimizu T, Miyata K, Nakamura M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Pharmacol Exp Ther. 1989 Aug;250(2):654-8.
The effect of a novel uricosuric diuretic, S-8666, on urinary excretion of Ca++ was investigated in conscious rats. S-8666 acts mainly on the thick ascending limb of Henle's loop. Oral administration of S-8666 (3.2-316 mg/kg), furosemide (10-316 mg/kg) and trichlormethiazide (TCM; 0.01-10 mg/kg) caused natriuresis in a dose-dependent manner. However, the dose-response relationships for Ca++ and Na+ excretion differed slightly among these drugs. Na+ excretion was enhanced to the same extent by both S-8666 and furosemide, whereas Ca++ excretion induced by S-8666 was much smaller than that induced by furosemide. In the TCM group, there was no correlation between urinary excretion of Na+ and Ca++, but this was, if anything, a negative correlation. In the furosemide group, there was a highly significant positive correlation between these parameters with the slope of the regression line being 0.30 (g/Eq). In the S-8666 group, there was positive correlation between these parameters, but the slope of the regression line (0.13) was significantly lower than that in the furosemide group. The pattern of urinary Ca++ excretion as normalized by Na+ in the S-8666 group was intermediate between those of the TCM and furosemide groups. These results are compatible with the hypothesis that S-8666 has an additional site of action which is common to that of thiazide diuretics.
在清醒大鼠中研究了新型促尿酸排泄利尿剂S-8666对Ca++尿排泄的影响。S-8666主要作用于髓袢升支粗段。口服S-8666（3.2 - 316 mg/kg）、呋塞米（10 - 316 mg/kg）和三氯噻嗪（TCM；0.01 - 10 mg/kg）均呈剂量依赖性地引起利钠作用。然而，这些药物之间Ca++和Na+排泄的剂量反应关系略有不同。S-8666和呋塞米使Na+排泄增加的程度相同，而S-8666诱导的Ca++排泄远小于呋塞米诱导的Ca++排泄。在TCM组中，Na+和Ca++的尿排泄之间无相关性，但如果有任何相关性的话，也是负相关。在呋塞米组中，这些参数之间存在高度显著的正相关，回归线斜率为0.30（g/Eq）。在S-8666组中，这些参数之间存在正相关，但回归线斜率（0.13）显著低于呋塞米组。S-8666组中经Na+标准化后的尿Ca++排泄模式介于TCM组和呋塞米组之间。这些结果与S-8666具有与噻嗪类利尿剂共同的额外作用位点这一假设相符。
