1570 HYDROCHLOROTHIAZIDE, AMILORIDE AND TOLMETIN IN THE TREATMENT OF DIABETES INSIPIDUS OF BRATTLEBORO RATS

Abstract

To test the effects of hydrochlorothiazide (HCTZ) alone and in combination with amiloride or tolmetin in the treatment of nephrogenic diabetes insipidus, metabolic studies of 12 days each were carried out in 36 male, Brattleboro rats. They were divided into five groups as follows: (A) controls; (B) high dose HCTZ at 6.0 mg/rat/day; (C) low dose HCTZ at 3.0 mg/rat/day; (D) HCTZ identical to (C) but with addition of amiloride at 0.6 mg/rat/day; (E) HCTZ identical to (C) but with addition of tolmetin at 40 mg/rat/day. The immediate response to treatment was a significant increase in urinary sodium excretion from mean values (mEq/kg/day) of less than 11 to higher than 13, except group E with value of 12. There was marked increase in urinary potassium excretion, (mEq/kg/day) from mean control value of 15.5 to 21.5, 20.8, 18.5, 17.7 in groups B, C, D and E respectively. During the last three days of the study, mean urine osmolality (Uosm) in mOsm/kg H2O and free water reabsorption (TCH2O) in ml/mm/kg BW increased significantly:These indices were higher in groups B, D and E than in group C. Serum osmolality decreased only in groups B, C and D but not in the HCTZ-tolmetin group. We conclude that these agents may eventually prove to be satisfactory alternative therapies in nephrogenic diabetes insipidus.