Diabetes-induced albuminuria: role of antidiuretic hormone as revealed by chronic V2 receptor antagonism in rats.
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.
Bardoux
Pascale
P
INSERM Unité 367, Institut du Fer à Moulin and INSERM Unité 430, Hôpital Broussais, Paris, France.
Bruneval
Patrick
P
Heudes
Didier
D
Bouby
Nadine
N
Bankir
Lise
L
D000419:Albuminuria / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology; D013311:Streptozocin; D014667:Vasopressins / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; D014667:Vasopressins; D013311:Streptozocin; C103281:satavaptan