Decreased renal excretion of uric acid following diuretic administration in rats.
In order to evaluate the cause of diuretic-induced hyperuricemia which has been well documented in clinical studies, clearance experiments were performed in rats using furosemide and trichlormethiazide . The net flux in the tubular transport of uric acid was reabsorptive, and the fractional excretion of uric acid responded sensitively to the transtubular transport inhibitors, sodium probenecid and pyrazinoic acid. When the hemoconcentration was induced by highly potent doses of test diuretics, the inulin clearance and the fractional excretion of uric acid clearly decreased. The contraction of body fluid produced by intraperitoneal administration of polyethylene glycol resulted in marked decrease of inulin clearance and fractional excretion of uric acid. The decrease of uric acid excretory capacity under the treatment with trichlormethiazide was completely corrected by saline loading. Moreover, no significant change was found in the pyrazinoic acid-suppressible fractional excretion of uric acid between the diuretic-treated rats and the control animals. These studies suggest that furosemide- and trichlormethiazide -induced changes in the renal handling of uric acid are mediated by the fluid volume contraction and that the decrease in fractional excretion of uric acid by test diuretics is the result of reabsorptive enhancement of uric acid.
D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000652:urine; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014237:Trichlormethiazide / Q000494:pharmacology; D014527:Uric Acid / Q000097:blood / Q000652:urine*
D004232:Diuretics; D007328:Insulin; D014527:Uric Acid; D011718:Pyrazinamide; C005296:pyrazinoic acid; D005665:Furosemide; D011339:Probenecid; D014237:Trichlormethiazide