Prevention of the progression of renal injury in diabetic rodent models with pre-existing renal disease with chronic endothelin A receptor blockade.

Prevention of the progression of renal injury in diabetic rodent models with pre-existing renal disease with chronic endothelin A receptor blockade. Am J Physiol Renal Physiol. 2018 May 30;: Authors: Spires D, Poudel B, Shields CA, Pennington A, Fizer B, Taylor L, McPherson KC, Cornelius DC, Williams JM Abstract The endothelin (ET) system has emerged as a therapeutic target for the treatment of diabetic nephropathy (DN). The present study examined whether chronic endothelin A (ETA) receptor blockade with atrasentan prevents the progression of renal injury in two models of DN with pre-existing renal disease that exhibit an increased renal ET-1 system compared to non-diabetic rats: streptozotocin-treated Dahl salt-sensitive (STZ-SS) and Type-2 diabetic nephropathy (T2DN) rats. Nine week-old SS rats were treated with (STZ, 50 mg/kg, i.p.) to induce diabetes. After 3 weeks of diabetes, proteinuria increased to 353{plus minus}34 mg/day. The rats were then separated into two groups: (1) vehicle and (2) atrasentan (5mg/kg/day) via drinking water. After 6 weeks of treatment with atrasentan, MAP and proteinuria decreased by 12% and 40%, respectively, in STZ-SS rats. The degree of glomerulosclerosis and renal fibrosis was significantly reduced in the kidneys of atrasentan-treated STZ-SS rats compared to vehicle STZ-SS rats. Interestingly, treatment with atrasentan did not affect GFR but significantly increased RBF by 33% and prevented the elevations in FF and RVR ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
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Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
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Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
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