The Changes of Aquaporin-2 Expression in Rats with Lithium Induced Nephrogenic Diabetes Insipidus after Hydrochlorothiazide Administration

Background:Thiazides have been used in nephrogenic diabetes insipidus (NDI) patients to decrease urine volume, but the mechanism of antidiuretic effect is not known yet. Recently, it has been demonstrated that abundance of aquaporin-2 (AQP2) was decreased in lithium induced NDI. We performed this study to investigate the effect of hydrochlorothiazide (HCTZ) in lithium induced NDI rats and the change of AQP2 expression. Methods:NDI was induced in 7 male Spraque- Dawley rats by feeding lithium carbonate containing rat chow (40 mmol/kg) for 5 weeks. 4 rats were control group. HCTZ 3.75 mg/day (n=3 among lithium treated; Li＋TZ) or vehicle (n=4 among lithium treated and control; Li and Control, respectively) was infused to the rats through osmotic minipump for the last 7 days. Urine volume and urine osmolality were measured. Kidneys were processed for immunohistochemistry and immunoblotting using antibody to AQP2. Results:Li＋TZ showed decreased urine volume (4611 mL/day for Li＋TZ vs. 1271 mL/day for Li, p139 mmol/kg for Li＋TZ vs. 2079 mmol/kg for Li, p2% for Li＋TZ vs. 209% for Li, p