Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent

Abstract

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-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.

© 2011 by the American Society of Nephrology

Figures

Figure 1.

Interaction between amiloride and the dDAVP effects on urinary sodium excretion. Forty-seven patients received twice a single intravenous dose of dDAVP (4 μg injected over 30 seconds) followed by a 2-hour continuous infusion of 4 μg of dDAVP in 50 ml isotonic saline solution alone (day 4) or after a 7-day administration of 20 mg o.d. amiloride (day 14). The left panel shows the individual UNaV. The box plot in right panel shows changes from baseline in UNaV (box, median and IQR; whiskers, 95% CI). UNaV, urine sodium excretion rate; *P < 0.05; $, significant interaction between amiloride and dDAVP effects (P < 0.10).

Figure 2.

Effect of dDAVP on urine potassium excretion rate (1) and (2) urinary Na/K ratio in the presence or absence of amiloride pretreatment (individual data of the 47 patients). ***P < 0.0001 dDAVP versus baseline.