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      Prevention of Renal Injury in Diabetic MWF Rats by Angiotensin II Antagonism

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          We studied the effect of the combination of streptozotocin-induced diabetes and spontaneous renal injury in male MWF rats. Renal hemodynamics was studied by micropuncture 1 month after streptozotocin administration, and kidney morphological evaluation was performed after 4 months of diabetes. We also studied the effect of angiotensin II antagonism on development of renal lesions. Untreated animals developed mild hypertension, proteinuria, and glomerulosclerosis. Induction of diabetes, and maintenance of a moderate hyperglycemic state, was associated with slight but significant elevation in systemic and glomerular capillary blood pressure. Development of proteinuria was not accelerated or exacerbated by diabetes. Glomerular and tubular structural changes were also not worsened by diabetes. Antihypertensive treatment with an ACE inhibitor (benazepril) or with an AII receptor antagonist (valsartan) almost completely prevented systemic and glomerular capillary hypertension, proteinuria and renal structural changes. No significant differences in glomerular volume were observed among the four groups. That induction of experimental diabetes, although associated with glomerular capillary hypertension, did not aggravate the rate of progression of renal dysfunction would suggest that glomerular injury is not directly influenced by glomerular hemodynamic conditions in these animals. Prevention of renal functional and structural abnormalities by antagonism of AII activity in diabetic MWF rats suggests a pathogenetic role for angiotensin in inducing the renal disease in these animals.

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          The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies.


            Author and article information

            Nephron Exp Nephrol
            Cardiorenal Medicine
            S. Karger AG
            February 1998
            04 February 1998
            : 6
            : 1
            : 28-38
            a Department of Kidney Research, Mario Negri Institute for Pharmacological Research, and b Division of Nephrology and Dialysis, Ospedali Riuniti di Bergamo, Italy
            20502 Exp Nephrol 1998;6:28–38
            © 1998 S. Karger AG, Basel

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            Figures: 4, Tables: 3, References: 49, Pages: 11
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