Effect of cilnidipine on renal function in SHR and endothelin-induced renal dysfunction.

Effect of cilnidipine (CIL) on renal function in SHR were evaluated in comparison with that of nifedipine (NIF) and nicardipine (NIC). In conscious SHR, CIL (3 and 10 mg/kg, p.o.) increased the urine volume, urinary Na+ excretion and urinary Na+/K+ ratio. NIF (3 and 10 mg/kg, p.o.) and NIC (10 mg/kg, p.o.) also increased the urine volume and urinary Na+ excretion, but not the urinary Na+/K+ ratio. In anesthetized SHR, CIL (3 and 10 micrograms/kg, i.v.) and NIF (10 micrograms/kg, i.v.) elevated the renal blood flow (RBF), but NIC did not. CIL (10 micrograms/kg, i.v.) also increased the glomerular filtration rate (GFR), whereas NIF did not. Furthermore, we investigated the effect of these three drugs on endothelin (ET)-induced renal dysfunction in anesthetized SHR. ET (2 micrograms/kg, i.v. +30 ng/kg/min) prolongly reduced RBF, GFR and urine volume by 47, 60 and 48%, respectively. CIL (1-10 micrograms/kg, i.v.) improved the decrease in RBF and urine volume induced by ET as well as NIF and NIC. When blood pressure was lowered to the similar extent among the three drugs in ET-treated SHR, CIL increased the RBF and urine volume compared with the others. NIF and NIC did not affect the reduction in GFR by ET, but CIL (0.3-3 micrograms/kg, i.v.) significantly increased GFR. These results suggest that CIL, NIF and NIC all have natriuretic action and no suppressive action on renal function in SHR. In addition, CIL has an ameliorative effect on renal dysfunction in ET-treated SHR, suggesting that CIL might improve renal dysfunction not only in hypertensive patients but also in those with acute renal failure.