| Abstract: | The effect of consecutive treatments with thiazide diuretics on renal handling of uric acid was investigated with clearance experiments using rats. Two weeks of oral administration of trichlormethiazide (2 mg/kg, twice a day) in rats fed an ordinary diet caused no change in the uric acid excretory capacity. However, a week of oral administration of trichlormethiazide (0.1, 0.5 and 2 mg/kg, twice a day) in rats maintained on a purified diet containing low sodium amounts decreased the fractional excretion of uric acid. At 2 mg/kg, the decrease of inulin clearance developed clearly. Similar treatments with hydrochlorothiazide (10 mg/kg) and cyclopenthiazide (0.5 mg/kg) also decreased the inulin clearance and the fractional excretion of uric acid. Administration of the above diuretics during sodium deprivation resulted in a marked rise of the hematocrit and hypokalemia. Purified diet containing low sodium amounts alone did not change the uric acid excretory capacity as compared to the ordinary diet. Trichlormethiazide treatment and continued sodium deprivation caused marked losses of body weight and food intake and promotions of urine output and water intake. Histologically, hyperplasia of the cells and tubular dilatation at macula densa were slightly developed during sodium deprivation. With these severe changes, dilatation of the proximal tubules with flattened and regenerated epithelium was shown by the trichlormethiazide treatment (0.5 mg/kg). From these results, the characteristics of chronic treatment with thiazide diuretics acting on renal uric acid retention could be understood in the rat under sodium deprivation. |
