Effects of a calcium antagonist, manidipine, on progressive renal injury associated with mild hypertension in remnant kidneys

Abstract

The present study was conducted to determine the effects of a calcium antagonist, manidipine, on the outcome of a remnant kidney model of chronic renal failure in Fisher 344 rats. After sham operation or five-sixths nephrectomy (Nx), the rats were assigned to one of the following groups according to the administered amount of drug and were provided a specified diet for 12 weeks: group 1 (sham), diet without manidipine; group 2 (Nx), diet without manidipine; group 3 (Nx), diet with 0.0004% manidipine; group 4 (Nx), diet with 0.002% manidipine; group 5 (Nx), diet with 0.01% manidipine; group 6 (Nx), diet with 0.05% manidipine. All diet contained the same amount of calories (3.44 kcal/gm) and protein (25% casein). Systolic blood pressure and urinary protein excretion in group 2 began to increase at 8 and 4 weeks after ablation, respectively. Manidipine attenuated the increase in blood pressure in groups 4 through 6 but not in group 3. Manidipine-treated groups 3 to 5 had significantly less proteinuria than group 2. Group 6 had significantly more proteinuria than group 2. At 12 weeks after ablation, the kidneys from group 2 showed severe parenchymal damage, which is characteristic of end-stage renal pathology. These changes were ameliorated in groups 3 through 5, while group 6 had significantly more injured renal pathology than group 2.(ABSTRACT TRUNCATED AT 250 WORDS)