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Abstract

The present investigation was undertaken to study the effect of chronic treatment with angiotensin (AT1) receptor antagonist losartan (2 mg/kg, p.o., 6 weeks) on streptozotocin (STZ) induced (45 mg/kg, i.v., single dose) renal dysfunctions in diabetic rats. Injection of streptozotocin produced not only the cardinal symptoms of diabetes mellitus like loss of body weight, hyperglycemia, and hypoinsulinemia but also the renal dysfunctions. Losartan treatment significantly prevented all these changes except STZ-induced hypoinsulinemia. There was a significant elevation of blood pressure in diabetic rats and treatment with losartan significantly brought it back to normal. Renal dysfunction in diabetic rats was characterized by a significant decrease in creatinine clearance, elevated levels of electrolytes and renal hypertrophy. Treatment with losartan prevented these changes. A good correlation was found between biochemical parameters and histopathological abnormalities. Our data suggests that, losartan may be considered as the drug of choice when there is a co-existence of diabetes mellitus and hypertension with compromised kidney function.

Enhanced Effect of Combined Treatment with SMP-534 (Antifibrotic Agent) and Losartan in Diabetic Nephropathy

“…Hence, to prevent progression of diabetic nephropathy, systemic and glomerular pressures must be controlled using angiotensin-converting enzyme inhibitors (ACEIs), angiotensin I receptor blockers (ARBs), etc. Many studies have demonstrated the efficacy of ACEIs and ARBs on nephropathy models, including a model of diabetic nephropathy [9, 10]. In addition, recent clinical studies of ACEIs [11] and ARBs [12, 13] have revealed that these agents exhibit renoprotective effects, including preventing the progression of nephropathy with reducing urine protein.…”