Administration of
urea to patients with the syndrome of inappropriate antidiuresis (SIAD) is thought to ameliorate
hyponatremia by both producing an osmotic diuresis and diminishing ongoing natriuresis. The present study evaluated these effects in a rat model of SIAD utilizing dilutional
hyponatremia induced by continuous infusion of 1-deamino-[8-D-
arginine] vasopressin. Following 48 hours of sustained
hyponatremia, separate groups of rats were then refed with either: (1) 5%
dextrose alone, (2) a 20%
protein chow, (3) an isocaloric
protein deficient (0%) chow, or (4) the isocaloric
protein-deficient chow supplemented with oral
urea. Our results demonstrate that rats refed a 20%
protein diet significantly improved their plasma [Na+] as compared to rats refed
protein deficient diets, and this improvement was accompanied by decreases in natriuresis despite an increased glomerular filtration rate and an unchanged negative free water clearance. Identical effects were observed in rats refed a
protein deficient diet but supplemented with oral
urea, suggesting that
urea generation from catabolism of
dietary protein is responsible for the effect of
protein refeeding to decrease urinary
sodium excretion. Both the
protein and
urea refed rats had significantly higher inner medullary
urea contents and concentrations compared to rats refed
protein-deficient diets and also to rats studied immediately before
protein refeeding, supporting the hypothesis that
urea and
dietary protein decrease natriuresis in patients with SIAD in association with increased inner medullary
urea concentrations.