BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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 diabeticrats (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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Manal Mazloum; Jordan Jouffroy; François Brazier; Christophe Legendre; Antoine Neuraz; Nicolas Garcelon; Dominique Prié; Dany Anglicheau; Frank Bienaimé Journal: J Am Soc Nephrol Date: 2019-06-19 Impact factor: 10.121
Authors: Ray El Boustany; Irina Tasevska; Esther Meijer; Lyanne M Kieneker; Sofia Enhörning; Guillaume Lefèvre; Kamel Mohammedi; Michel Marre; Frédéric Fumeron; Beverley Balkau; Nadine Bouby; Lise Bankir; Stephan Jl Bakker; Ronan Roussel; Olle Melander; Ron T Gansevoort; Gilberto Velho Journal: JCI Insight Date: 2018-07-12
Authors: Giovanna Muscogiuri; Luigi Barrea; Giuseppe Annunziata; Martina Vecchiarini; Francesco Orio; Carolina Di Somma; Annamaria Colao; Silvia Savastano Journal: Endocrine Date: 2018-07-19 Impact factor: 3.633
Authors: Richard J Johnson; Bernardo Rodriguez-Iturbe; Carlos Roncal-Jimenez; Miguel A Lanaspa; Takuji Ishimoto; Takahiko Nakagawa; Ricardo Correa-Rotter; Catharina Wesseling; Lise Bankir; Laura G Sanchez-Lozada Journal: Nat Rev Nephrol Date: 2014-05-06 Impact factor: 28.314