Diabetes-induced albuminuria: role of antidiuretic hormone as revealed by chronic V2 receptor antagonism in rats.

Abstract

Vasopressin, an antidiuretic hormone, is elevated in diabetes mellitus (DM). The aim of this study was to evaluate whether the V(2) receptor-mediated actions of vasopressin contribute to the albuminuria of diabetes. Fourteen adult male Wistar rats with streptozotocin-induced DM were treated over 9 weeks with a selective, non-peptide, orally active V(2) receptor antagonist (SR 121463) and were compared to 14 untreated diabetic rats (control). The dose of antagonist was adapted in order to maintain urine osmolality close to plasma osmolality, but not to induce the formation of hypoosmotic urine. Every second week, urine was collected in metabolic cages for two 24 h periods. Urinary albumin excretion (UAE) rose regularly and significantly with time in the untreated control group, whereas it did not rise in treated rats. Interestingly, a variable pattern of UAE increase over time was observed in different rats of the control group. Some rats exhibited pronounced progression of albuminuria with time, while others showed no or only a very modest rise. An a posteriori partition of the control group into 'progressors' and 'non-progressors' revealed that progressors had more intense urinary concentrating activity, higher creatinine clearance and larger relative glomerular mesangial area than the other subgroup. This study shows that V(2) receptor-mediated actions of vasopressin play a critical role in the albuminuria of diabetes. It also reveals that individual rats, like humans, seem to exhibit an unequal susceptibility to diabetic nephropathy, or at least to albuminuria, a factor considered to be one of its early manifestations.