Nephrol Dial Transplant (2003) 18: 497-506
© 2003 European Renal Association-European Dialysis and Transplant Association
Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin–angiotensin system
1 INSERM Unité 367, Institut du Fer à Moulin, Paris, France,
2 Centre de Recherche, Hôpital du Sacré-C
ur, Université de Montréal, Montréal, Canada and
3 Groupe Hospitalier Bichat–Claude Bernard, Service de Diabétologie, Endocrinologie, Métabolisme, Paris, France
Background. An increase in urinary albumin excretion (UAE) represents an early predictor of glomerular damage in diabetes mellitus (DM) and a risk factor for cardiovascular complications in hypertension. Vasopressin is elevated in DM and in some forms of hypertension. Previous studies in rats suggested that this hormone could play a role in the albuminuria observed in chronic renal failure or diabetic nephropathy, but no information is available concerning the mechanism of these effects and the possible influence of vasopressin on UAE in the healthy kidney. The present study was thus designed to evaluate whether vasopressin influences UAE in normal rats and humans, whether this effect is V2-receptor-dependent, and whether it is mediated by the renin–angiotensin system.
Methods. UAE was measured in normal Wistar rats and healthy humans, or in subjects with various forms of diabetes insipidus (DI), before and after acute or chronic infusion of the vasopressin V2 receptor agonist dDAVP®. Chronic dDAVP administration was also performed in normal Wistar rats previously submitted to either chronic angiotensin-converting enzyme inhibition (ACEI) or chronic blockade of AT1 receptors (ARB).
Results. In rats, acute or chronic dDAVP infusion increased UAE significantly and reversibly (4-fold and 6-fold, respectively). In healthy subjects, acute infusion of dDAVP tripled UAE (P<0.01) but did not change creatinine and ß2-microglobulin excretion, thus suggesting that the rise in UAE was due to an increased glomerular leakage of albumin. dDAVP also increased UAE in patients with central DI and in patients with hereditary nephrogenic DI bearing AQP2 mutations. However, UAE was not increased in patients with hereditary nephrogenic DI bearing mutations of the V2 receptor. In rats, ACEI and ARB blunted the dDAVP-induced rise in UAE by 70% (P<0.05) and 50% (NS), respectively.
Conclusions. The present studies reveal for the first time that vasopressin induces a marked increase in UAE in healthy rats and humans. This albuminuric effect seems to result from increased glomerular leakage, requires functional vasopressin V2 receptors, and is, at least in part, mediated by the renin–angiotensin system. These results bring additional support for an involvement of vasopressin in the albuminuria observed in pathological states such as diabetes mellitus or hypertension.
Keywords: ACE inhibition; angiotensin II receptor blockade; blood pressure; diabetes insipidus; diabetes mellitus; microalbuminuria
Correspondence and offprint requests to: L. Bankir, INSERM Unit 367, 17 Rue du Fer à Moulin 75005 Paris, France.Email: bankir{at}ifm.inserm.fr
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