title: Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system.
abstract: 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 V(2)-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 V(2) 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 beta(2)-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 V(2) 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 V(2) 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.
authors.affiliation: INSERM Unité 367, Institut du Fer à Moulin, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bardoux
authors.forename: Daniel Georges
authors.initials: DG
authors.lastname: Bichet
authors.forename: Hélène
authors.initials: H
authors.lastname: Martin
authors.forename: Yves
authors.initials: Y
authors.lastname: Gallois
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Arthus
authors.forename: Michèle
authors.initials: M
authors.lastname: Lonergan
authors.forename: Nicole
authors.initials: N
authors.lastname: Ruel
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000139:chemically induced* / Q000503:physiopathology* / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003894:Deamino Arginine Vasopressin / Q000009:adverse effects*; D003919:Diabetes Insipidus / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D017483:Receptors, Vasopressin / Q000502:physiology*; D012016:Reference Values; D012076:Renal Agents / Q000009:adverse effects*; D012084:Renin-Angiotensin System / Q000502:physiology*; D014667:Vasopressins / Q000009:adverse effects*
chemical_list: D017483:Receptors, Vasopressin; D012076:Renal Agents; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin