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Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent #MMPMID21233458
Blanchard A; Frank M; Wuerzner G; Peyrard S; Bankir L; Jeunemaitre X; Azizi M
Clin J Am Soc Nephrol 2011[Apr]; 6 (4): 753-9 PMID21233458show ga
BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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-mug intravenous bolus followed by 4 mug 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.