Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of diabetic nephropathy in a mouse model of type 2 diabetes

Abstract Aims Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse m... Full description

Abstract Aims Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse model of type 2 diabetes. Methods Male obese diabetic db/db mice were treated for 12 weeks with a selective V2R antagonist ( SR121463 ) and compared to non-treated db/db and non-diabetic db/m mice. All animals were previously uninephrectomized. Results The V2R antagonist did not alter glycemia or glycosuria in db/db mice. It induced a two-fold increase in urine output and a 52% decrease in urine osmolality compared to non-treated db/db mice. After four weeks of treatment urinary albumin to creatinine ratio was 50% lower in treated mice compared to non-treated mice, and remained significantly lower until end of experiment. Glomerular filtration rate increased significantly over time in non-treated db/db mice but remained stable in treated mice. Conclusions This study shows that vasopressin contributes to albuminuria and glomerular hyperfiltration via V2R in a mouse model of type 2 diabetes. It documents causality behind the association of vasopressin with renal disease observed in diabetic patients.