title: Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent.
abstract: OBJECTIVE
  Acute infusion of the potent V2 receptor agonist 1-desamino-8-d-arginine vasopressin (dDAVP) reduces sodium excretion in humans, through an effect attributed to the stimulation of the amiloride sensitive epithelial sodium channel, ENaC, in ex vivo/in vivo experiments. We investigated in humans whether the antinatriuretic effect of dDAVP is sensitive to amiloride, a specific blocker of ENaC.
  
  
  METHODS
  Forty-eight healthy normotensive adult men were assigned to a high Na/low K (250/40 mmol/d) diet, to suppress aldosterone secretion. dDAVP (4-μg intravenous bolus followed by 4 μg over 2 hours) was administrated before and after a 7-day administration of 20 mg/d amiloride. Urine and blood samples were collected before and at the end of the dDAVP infusion, to measure Na, K, creatinine, and osmolality concentrations.
  
  
  RESULTS
  dDAVP alone decreased the urinary flow rate by 75% and the sodium excretion rate by 19% despite an increase in creatinine clearance by 38 ml/min. Potassium excretion rate was unchanged and the urinary Na/K ratio decreased by 18%. Seven-day amiloride administration had no effect on the dDAVP-induced decrease in the urinary flow rate (-71%) nor on the dDAVP-induced increase in creatinine clearance (+35 ml/min), but it fully prevented the dDAVP-induced decrease in both urinary sodium excretion (+1%) and urinary Na/K ratio (+21%).
  
  
  CONCLUSIONS
  The antinatriuretic effect of dDAVP in humans is amiloride sensitive, and thus is related to the stimulatory effect on ENaC-mediated sodium reabsorption. This test provides a new tool to investigate ENaC function in a clinical setting.
authors.affiliation: Centre d'Investigations Cliniques, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris Cedex 15, France. anne.blanchard@egp.aphp.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Michael
authors.initials: M
authors.lastname: Frank
authors.forename: Grégoire
authors.initials: G
authors.lastname: Wuerzner
authors.forename: Severine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
mesh_terms: D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D053503:Epithelial Sodium Channels / Q000502:physiology*; D006801:Humans; D008297:Male; D045283:Natriuretic Agents / Q000494:pharmacology*; D017419:Potassium, Dietary / Q000008:administration & dosage; D017483:Receptors, Vasopressin / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage
chemical_list: D053503:Epithelial Sodium Channels; D045283:Natriuretic Agents; D017419:Potassium, Dietary; D017483:Receptors, Vasopressin; D012982:Sodium, Dietary; D000584:Amiloride; D012964:Sodium; D003894:Deamino Arginine Vasopressin