Dual blockade of Renin Angiotensin system in reducing the early changes of diabetic retinopathy and nephropathy in a diabetic rat model

Abstract

Background: Diabetes mellitus is a real pandemic of the modern world and the incidence of the disease is increasing at a tremendous rate with a number of complications involving major systems of the human body. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy and retinopathy.

Aim: The study was designed to evaluate and compare effects of ramipril (angiotensin-converting enzyme inhibitor-ACEI) and telmisartan (angiotensin II receptor blocker - ARBs) combinations on the progression of retinopathy and nephropathy in the streptozotocin (STZ) induced diabetic model.

Materials and methods: Diabetic state in rats was induced by chemical method using STZ 55 mg/kg intraperitoneally. Diabetic renal tubulopathy and interstitial inflammatory changes were done. Diabetic retinopathy manifested in the form of vacuolar changes in the inner plexiform and the ganglionic layers of the retina was observed.

Results: Treatments with ACEI and ARBs reduced the incidence of the occurrence of cataract. The effect of combinational drugs of ACEI (ramipril) and AT1 receptor blocker (Telmisartan) was evaluated. The drugs used in combinations showed improvement in the histopathological and biochemical changes of the diabetic animals, both for the retina and kidney.

Conclusion: The efficacy of the drugs suggests a pivotal role of the local RAS system in the pathogenesis of tubulopathy in the kidney and neuronal damage in the retina of the diabetic animals.

Keywords: Diabetes; Diabetic nephropathy; Dual block; Nephropathy; Ramipril; Renin angiotensin system; Retinopathy; STZ; Telmisartan.

Figure 1

H&E staining of kidney structure containing tubules, interstitium and glomerulus. H&E staining of kidney structure containing tubules, interstitium and glomerulus. C - control with normal tubules, interstitium and glomerulus. D - diabetic control with extensive tubular dilatation showing epithelial cell atrophy severe interstitial inflammations (not shown) and normal glomerulus. D1, D3, D6 shows moderate tubular dilatation with mild to moderate interstitial inflammations (not shown) and normal glomerulus. D5 photograph shows only mild tubular dilatation with mild interstitial inflammations and normal glomerulus. (magnification 400×)

Figure 2

H&E staining of layers of retina of control (C), diabetic (D) and the drug treated diabetic groups. H&E staining of layers of retina of control (C), diabetic (D) and the various drugs treated diabetic groups. The control group showed the orderly arrangement of all the cell layers of retina without any vacuolations. Diabetic group and D1, D2, D3, D4, D6 and D7 show extensive vacuolations in the inner plexiform layers and the ganglionic layer of the retina. In diabetic treated group (D5) vacuolations markedly reduced. (Magnification 400×)