Abstract
Effects of SE-1520 were compared with those of thiazide diuretics, hydrochlorothiazide (HCT) and trichlor-methiazide (TCM) in rats and dogs. SE-1520 in an oral dose of 0.1 ?? 10.0 mg/kg resulted in a strong and dose-dependent increase in urine volume as well as in the urinary excretion of Na+ and Cl-, while that of K+ significantly increased with an oral dose over 3.0 mg/kg. In experimental acidotic, alkalotic, nephritic and spontaneously hypertensive rats, almost the same strong natriuretic activity seen in normal rats was observed with SE-1520. The diuretic potency of these three diuretics in rats was MCT≥SE-1520>HCT. SE-1520 also exhibited a strong diuretic activity in dogs. In the renal clearance test of dogs, SE-1520 0.1 ?? 1.0 mg/kg i.v. did not influence the renal plasma flow (RPF) or glomerular filtration rate (GFR). The renal tubular Na+ reabsorption rate decreased by a maximum of 2.11% and the urinary Na+ excretion increased by 15.3 times the normal level 20 min after the injection of SE-1520 in a dose of 1.0 mg/kg i.v. From the results of clearance test and stop flow test in dogs, the site of action of SE-1520 was observed to be mainly in the distal tubules.
