DIETARY-SODIUM INFLUENCES THE RENAL EFFECTS OF THEOPHYLLINE

Several previous observations support the hypothesis that endogenous l evels of adenosine in the kidney are directly related to dietary Na in take. If this hypothesis is true, then theophylline, a competitive ade nosine receptor antagonist, should produce more intense renal effects in Na-loaded than in Na-deprived animals. In the present experiments, renal hemodynamics and renal tubular functions were assessed by cleara nce techniques in three groups of anesthetized rats--previously fed ei ther high, normal, or low Na diets for at least three weeks--before an d during theophylline administration (55.5 mumol kg-1 prime and 0.555 mumol kg-1 min-1 infusion, i.v.). Theophylline increased filtration fr action (ratio of inulin to para-aminohippurate clearances), urine flow and Na excretion in all three groups, but contrary to the hypothesis, the effects were smaller in Na-loaded than in Na-deprived rats. This relative insensitivity of the Na-loaded rats was not due to extremely high levels of endogenous adenosine, because the theophylline-induced changes were not potentiated either by doubling the dose of theophylli ne or by infusing adenosine deaminase (5 units kg-1 min-1) to destroy endogenous adenosine. Collectively, these observations are inconsisten t with the hypothesis that endogenous levels of adenosine in the kidne y are higher in Na-loaded than in Na-deprived rats.