EFFECTS OF NZ-105, A NEW CALCIUM-ANTAGONIST, ON RENAL-FUNCTION IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

The effects of a new dihydropyridine derivative, NZ-105, on renal function were investigated in anesthetized spontaneously hypertensive rats. Intravenous injection of NZ-105 (0.01 and 0.03 mg/kg of body weight) significantly increased the urine flow rate (UV) and renal absolute excretion of sodium and chloride. Potassium excretion also increased significantly, but it was relatively slight in comparison with sodium or chloride excretion. There was a decrease in mean blood pressure (-14.5 +/- 2.3 and -22.3 +/- 3.4 mm Hg, 20 min after the administration of 0.01 and 0.03 mg/kg of body weight, respectively). The glomerular filtration rate (GFR) was not changed; however, the renal plasma flow (RPF) was significantly increased. The tubular site of action of NZ-105 was investigated by the lithium clearance technique. Intravenous injection of NZ-105 inhibited sodium reabsorption beyond the proximal tubules about four to five times more effectively than at the proximal tubules. In conclusion, intravenous administration of NZ-105 in anesthetized spontaneously hypertensive rats caused diuretic and natriuretic action: The possible site of diuretic action may be mainly at the nephron segments beyond the proximal tubules.