Work

Absence of ETA receptors on podocytes is not antialbuminuric in diabetic mice

Year: 2013

Type: article

Abstract: Endothelin-1 (ET-1) has been shown to have an important role in diabetic nephropathy (DN).Here we investigated the contribution of endothelial cell-derived ET-1 to the changes in renal phenotype of diabetic mice.Therefore, we induced type 1 diabetes in vascular endothelial cell-specific ET-1 knockout (VEETKO) mice and their wild type (WT) littermates by streptozotocin injection (i.p.50 mg/kg/day, five consecutive days).After ten and 22 weeks of diabetes, we observed an increase of food and water intake, urine volume and creatinine clearance in both genotypes compared to non-diabetic mice.The renal cortical expression of ET-1 mRNA was not significantly activated by diabetes.Nevertheless, VEETKO mice showed only about half of ET-1 mRNA expression compared to WT mice.Though, there were no significant differences in the renal function including albumin and protein excretion between the genotypes.Based on hematocrit measurements, neither diabetes nor ET-1 deficiency had an impact on fluid retention.After ten weeks of diabetes, systolic blood pressure measured by tailcuff method decreased in WT mice.After 22 weeks, heart rate and systolic and diastolic blood pressure were similar between all groups.At baseline the kidneys of VEETKO mice were significantly heavier (+15%) compared to WT mice but this gap was not observed in diabetic condition.In contrast to previously presented data, in this model of type 1 diabetes we are not able to confirm the pivotal role of endothelial cell derived ET in the development of DN.

Source: Life Sciences

DOI: 10.1016/j.lfs.2013.12.083