Effect of S-8666 on urinary Ca++ excretion in rats

T Shimizu, K Miyata and M Nakamura

Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.

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.

Volume 250, Issue 2, pp. 654-658, 08/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics