EFFECTS OF BENIDIPINE ON RENAL-FUNCTION IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

Effects of benidipine on urine volume, excretion of electrolytes and renal hemodynamics were investigated in anesthetized spontaneously hypertensive rats (SHR). Benidipine at 3 and 10 mu g/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretion with no change of creatinine clearance (C-RE). The increase in K excretion was relatively slight when compared with that in Na excretion. In another series of experiments, the tubular sites of action of benidipine were determined by the lithium clearance (C-Li) technique and the stop-flow method. Benidipine at 3 mu g/kg (i.v.) increased C-Li, decreased creatinine concentration and increased Na concentration in the stop-flow urine from the distal nephron. These results suggest that benidipine produces diuresis and natriuresis by the inhibition of water and Na reabsorption at both the proximal tubule and the distal nephron. Benidipine increased p-aminohippuric acid clearance, but not C-CRE, at doses of 3 and 10 mu g/kg (i.v.), suggesting that benidipine dilates the glomerular efferent arteriole as well as the afferent arteriole. It is, therefore, expected that benidipine does not cause intraglomerular hypertension and has a beneficial effect in progressive renal disease.