A comparison of the uricosuric effects in rats of diltiazem and derivatives of dihydropyridine (nicardipine and nifedipine).
The effects of nicardipine and nifedipine on the urinary excretion of urate were examined in rats and compared with those of diltiazem. Test drugs were administered to urethane-anesthetized oxonate-loaded rats by continuous i.v. infusion. Diltiazem (10 micrograms/rat/min), nicardipine (0.3 microgram/rat/min) and nifedipine (1.0 microgram/rat/min) caused similar reductions of systemic blood pressure and increased total renal blood flow. Diltiazem did not increase urine volume significantly. However, this drug produced obvious uricosuria, with a significant increase in the ratio of urate clearance to inulin clearance (Cua/Cin), which resulted from an increase in Cua, but not from changes in the glomerular filtration rate (GFR). Nicardipine had clear diuretic and uricosuric effects, with similar increases in Cua and GFR and, thus, no change in Cua/Cin. On the other hand, nifedipine did not have any significant effect on the renal handling of urate. These results suggest that nicardipine produces uricosuria in rats via alterations in renal hemodynamics, while the uricosuric effect of diltiazem involves the tubules, as well as alterations in renal hemodynamics.
Sugino
H
H
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Shimada
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007444:Inulin / Q000652:urine; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D014527:Uric Acid / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
D014528:Uricosuric Agents; D014527:Uric Acid; D007444:Inulin; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine