ABSTRACT
The aim of this study was to investigate the role of amlodipine and diltiazem [calcium channel blockers] in the prevention and treatment of diabetic nephropathy in rats. Eighty male albino rats weighing [130-180 g] were used in this study. These animals were subdivided into five groups; Group I: control group, Group II: diabetic ischaemic rats treated with insulin for 12weeks, Group III: diabetic ischaemic rats treated with insulin and captopril for 12 weeks, Group IV: diabetic ischaemic rats treated with insulin and diltiazem for 12 weeks, Group V: diabetic ischaemic rats treated with insulin and amlodipine for 12 weeks. At the end of the experiments, urine and blood samples were obtained for biochemical analysis and kidney samples were taken for histopathological evaluation. Diabetes mellitus [DM] produced a significant increase in rat kidney weight, creatinine clearance and a highly significant increase in kidney/body weight [K/B] ratio, random blood glucose, 24 h urine volume and protein and serum creatinine. While renal ischaemia alone produced a significant increase in systolic blood pressure [SBP], BUN and serum creatinine, it produced a significant decrease in creatinine clearance. Combination of renal ischaemia with DM also produced a significant increase in rat kidney weight and BUN levels and a significant increase in K/B ratio, random blood glucose, 24-h urine volume and protein and creatinine concentration. Moreover, this combination produced a significant decrease in creatinine clearance. Insulin, when given alone produced a significant reduction of the enlarged rat kidney weight and elevated K/B ratio, blood glucose and 24-h urine volume. Treatment with diltiazem or amlodipine significantly lowered the elevated SBP and 24-h urine volume. Furthermore, treatment with captopril significantly lowered the elevated SBP, serum creatinine, K/B ratio and proteinuria. Light microscopic examination of kidneys from diabetic animals revealed glomerulopathy characterized by thickening of the glomerular basement membrane, mesangial matrix expansion, arteriole hyalinosis and large proteinaceous deposits occluding capillary loops and hyaline proteinaceous droplets within the glomeruli. Moreover, examination of the kidneys of ischaemic animals by light microscopy revealed focal tubular necrosis at multiple points along the nephron, and occlusion of tubular lamina by eosinophilic hyaline casts or pigmented granular casts particularly in distal tubules. There was an interstitial oedema and accumulation of leukocytes within the dilated vasa recta. Treatment with insulin alone did not reverse the histopathological changes. Treatment with captopril did not reverse the morphological changes in the glomeruli and the casts did not disappear. However, treatment with diltiazem and amlodipine improved many histopathological changes. In conclusion, diltiazem and amlodipine ameliorated the signs of diabetic nephropathy