Renal effects of indanone in dogs and rats: modification by a cyclooxygenase inhibition

The effects of indomethacin, a PG synthesis inhibitor, on the renal hemodynamic and diuretic responses to indanone were evaluated in 10 rats and 12 dogs. In anaesthetized rats, 50 mg/kg of indanone, an indanyloxyacetic acid diuretic, increased water excretion 20--30 times, sodium excretion 80--100 times, and potassium excretion 4 times, without marked changes in GFR and BP. Indomethacin pretreatment, 2 mg/kg, did not significantly reduce these responses. In vehicle pretreated dogs, urine flow, and sodium and potassium excretions increased 9,7 and 2 fold, respectively, after 4 mg/kg indanone. These responses were significantly diminished in dogs pretreated with 4 mg/kg indomethacin. Mean RBF was reduced 17% (P less than 0.02) after 10 min of indanone infusion (0.2 mg/kg/min). Indomethacin failed to alter this effect, suggesting the action of indanone differs from that of furosemide and ethacrynic acid, agents know to cause PG mediated renal vasodilation. The cyclooxygenase inhibitor did inhibit the diuretic response to indanone in these dogs. The dissimilar renal excretory response in the two species may reflect a more effective blockade by indomethacin of the tubular secretion of indanone in dogs than in rats. Alternatively, PGs may have different renal effects in the two species, or cyclooxygenase was inhibited to a greater extent in dogs than in rats.