Korean J Nephrol.  2004 Jan;23(1):5-11.

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

• Oh YK
• Lee JW
• Chang HR
• Park YS
• Kim GH
• Han JS
• Earm JH

Abstract

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 (46+/-11 mL/day for Li+TZ vs. 127+/-1 mL/day for Li, p<0.05) and higher urine osmolality (557+/-139 mmol/kgH2O for Li+TZ vs. 207+/-9 mmol/kgH2O for Li, p<0.05) comparing to Li. In semi-quantitative immunoblotting using whole kidney homogenate, Li+TZ showed increase in AQP2 expression comparing to Li (39+/-2% for Li+TZ vs. 20+/-9% for Li, p<0.05, % of normal controls). In immunohistochemistry, AQP2 expression in cortex was markedly decreased after lithium treatment. But, AQP2 expression was slightly increased after HCTZ treatment. CONCLUSION: HCTZ treatment partially increased urine concentrating ability and AQP2 expression in rats with lithium induced NDI. We concluded that partial improvement in urine concentrating ability might be associated with upregulation of AQP2.

Keyword

Hydrochlorothiazide; Lithium; Nephrogenic diabetes insipidus; Aquaporin-2

MeSH Terms

Animals
Antidiuretic Agents
Aquaporin 2*
Diabetes Insipidus, Nephrogenic*
Humans
Hydrochlorothiazide*
Immunoblotting
Immunohistochemistry
Kidney
Kidney Concentrating Ability
Lithium Carbonate
Lithium*
Male
Osmolar Concentration
Rats*
Thiazides
Up-Regulation
Antidiuretic Agents
Aquaporin 2
Hydrochlorothiazide
Lithium
Lithium Carbonate
Thiazides