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 mu g/rat/min), nicardipine (0.3 mu g/rat/min) and nifedipine (1.0 mu g/rat/min) caused similar re ductions of systemic blood pressure and increased total renal blood fl ow. Diltiazem did not increase urine volume significantly. However, th is drug produced obvious uricosuria, with a significant increase in th e ratio of urate clearance to inulin clearance (Cua/Cin), which result ed from an increase in Cua, but not from changes in the glomerular fil tration rate (GFR). Nicardipine had clear diuretic and uricosuric effe cts, with similar increases in Cua and GFR and, thus, no change in Cua /Cin. On the other hand, nifedipine did not have any significant effec t on the renal handling of urate. These results suggest that nicardipi ne 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.