In
lithium-induced
nephrogenic diabetes insipidus (NDI), alterations in renal medullary osmolyte concentrations have been assumed but never investigated.
Amiloride can modify
lithium-induced NDI, but the impact of
amiloride in
lithium-induced NDI on renal medullary osmolytes,
aquaporins, and
urea transporters is unknown and is the basis of this study. Rats fed
lithium (60 mmol/kg dry food) over 4 wk developed NDI. Urine osmolality fell to 287 +/- 19 mosmol/kgH(2)O (controls 1,211 +/- 90 mosmol/kgH(2)O). Organic osmolytes in the renal medulla showed significant decreases compared with controls [
inositol 221 +/- 35 to 85 +/- 10 mmol/kg
protein;
sorbitol 35 +/- 9 to 3 +/- 1 mmol/kg
protein;
glycerophosphorylcholine (GPC) 352 +/- 80 to 91 +/- 20 mmol/kg
protein; and
glycine betaine 69 +/- 11 to 38 +/- 38 mmol/kg
protein]. Medullary
urea content fell from 2,868 +/- 624 to 480 +/- 117 mmol/kg
protein. Concurrent administration of
amiloride (0.2 mmol/l) in the
drinking water restored urine osmolality (1,132 +/- 154 mosmol/kgH(2)O), and reduced urine volume. Medullary osmolyte content were restored to control values (
inositol, 232 +/- 12;
sorbitol 32 +/- 6; GPC, 244 +/- 26;
glycine betaine, 84 +/- 5 mmol/kg
protein). Medullary
urea rose to 2,122 +/- 305 mmol/kg
protein. Reduced AQP2, AQP3, and
urea transporter (UT-A1) expression was significantly reversed following
amiloride therapy. Data presented here provide further understanding of how
amiloride may substantially restore the
lithium-induced impaired renal concentrating mechanism.