A new diuretic that does not reduce renal handling of uric acid in rats, S-8666.

Abstract

Abstract-The uric acid-retaining effects of diuretics were studied using sodium restricted spontaneously hypertensive rats. Test agents were administered orally once a day for two weeks.Diuretic thiazides such as trichlormethiazide and hydrochlorothiazide and loop diuretics such as furosemide and indacrinone clearly reduced the renal function for uric acid excretion in treatment which produced major effects such as diuresis, saluresis and hypotension.However, a new diuretic with uricosuric activity, S-8666, developed in our laboratories, had no effect on the renal handling of uric acid at doses which showed major effects similar to those of other diuretics.The results should aid the understanding of the utility of S-8666 as a new diuretic antihypertensive which does not cause hyperuricemia during therapy.

Impact of sex and pathophysiology on optimal drug choice in hypertensive rats: Quantitative insights for precision medicine

“…We simulate the administration of a thiazide diuretic (TZD) by decreasing the fractional amount of sodium along the distal segment of the nephron by 50% and increasing the amount of renin secretion by 100%. This iScience Article results in a 0.88% G 0.20% decrease in plasma sodium concentration and a 2.07 G 0.08-fold increase in plasma renin activity in males, which is within range of experimental data reported for hydrochlorothiazide administered in male SHRs (Table 2) (Lai et al, 1982;Yonetani et al, 1987). As a result, simulated MAP decreases by 7.72% G 0.86% in males, which is consistent with experimental results (Table 2) (Lai et al, 1982;Yonetani et al, 1987).…”

“…(S99)). In order to calibrate the amount of reduction in sodium reabsorption in the distal segment, we fit the experimental plasma sodium concentration reported after administration of hydrochlorothiazide to SHRs (Yonetani et al 1987). And we calibrate the amount of increase in renin secretion by fitting to reports of plasma renin activity in experiments after administering hydrochlorothiazide to SHRs (Lai et al 1982;.…”

Impact of Sex and Pathophysiology on Optimal Drug Choice in Hypertensive Rats: Quantitative Insights for Precision Medicine

“…This iScience Article results in a 0.88% G 0.20% decrease in plasma sodium concentration and a 2.07 G 0.08-fold increase in plasma renin activity in males, which is within range of experimental data reported for hydrochlorothiazide administered in male SHRs (Table 2) (Lai et al, 1982;Yonetani et al, 1987). As a result, simulated MAP decreases by 7.72% G 0.86% in males, which is consistent with experimental results (Table 2) (Lai et al, 1982;Yonetani et al, 1987). Females have a much larger decrease in simulated MAP of 17.7% G 3.5% (see explanation below).…”

Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients

“…This may be because serum uric acid levels are more influenced by the uric acid production among subjects with preserved renal function than among those with CKD, in which serum uric acid increases owing to decreased urate excretion. Nevertheless, because serum uric acid is affected by various parameters including diuretic use that can affect urinary urate excretion [ 27 , 28 ], this possibility should be re-assessed in future studies based on larger study population.…”