PROTECTIVE EFFECT OF THE CALCIUM-ANTAGONIST NKY-722 AGAINST RENAL ANDARTERIAL INJURIES IN DAHL SALT-SENSITIVE RATS

Objective: To study the effect of long-term administration of NKY-722 and nicardipine on renal dysfunction and morphological changes in the kidneys and arteries in Dahl salt-sensitive (Dahl-S) rats. Design: Veh icle, NKY-722 and nicardipine were administered orally to Dahl-S rats fed a high-salt diet for 6 weeks. Methods: Systolic blood pressure was measured once a week. At the last week blood and urine were collected and an autopsy was carried out. Results: NKY-722 (1 mg/kg per day) lo wered blood pressure reproducibly for 6 weeks, whereas nicardipine (3 mg/kg per day) showed a similar effect at week 1 only. NKY-722 tended to decrease blood urea-nitrogen, and reduced plasma creatinine and ren in activity significantly. NKY-722 increased urine volume, urinary sod ium, creatinine and protein excretions, but did not affect urinary N-a cetyl-beta-D-glucosaminidase activity significantly. NKY-722 increased the glomerular filtration rate and reduced glomerulosclerosis and ren al arterial injury morphologically. Nicardipine did not affect blood o r urinary parameters, but reduced glomerular injury significantly. NKY -722 but not nicardipine reduced cerebral arterial injury. A lower dos e of NKY-722 (0.3 mg/kg per day) did not affect blood pressure, brood or urinary parameters, but reduced glomerulosclerosis and renal arteri al injury significantly. NKY-722 (1 mg/kg per day) and nicardipine (3 mg/kg per day) increased urinary 6-keto-prostaglandin F-1 alpha, (6-ke to-PGF(1 alpha)) and PGE(2). NKY-722 but not nicardipine increased the 6-keto-PGF(1) alpha:thromboxane B-2 ratio in the thoracic aorta. Conc lusions: NKY-722 improved the renal dysfunction, and reduced glomerula r, renal and cerebral arterial injuries in Dahl-S rats. The effect of NKY-722 on glomerulosclerosis and arterial injuries is, at least partl y, independent of blood pressure, and is probably related to the effec t on eiconsanoid metabolism.