EVIDENCE IN HYPONATREMIA RELATED TO INAPPROPRIATE SECRETION OF ADH THAT V-1 RECEPTOR STIMULATION CONTRIBUTES TO THE INCREASE IN RENAL URIC-ACID CLEARANCE

In hyponatremia related to syndrome of inappropriate antidiuretic horm one (SIADH), hypouricemia is explained primarily by the high uric acid clearance rate that results from the decrease in tubular uric acid re absorption, This modification of tubular handling of uric acid is cons idered to be induced by the increase in the ''effective vascular volum e.'' This study was designed to determine if V-1-receptor stimulation participates in the development of a high uric acid clearance rate as in SIADH, in which the antidiuretic hormone acts on V-1 and V-2 recept ors, Therefore, the urate clearance rate was measured in seven volunte ers with 1-desamino-8-D-arginine vasopressin (dDAVP)-induced hyponatre mia, with dDVAP stimulating exclusively the V-2 receptors (Group I), a nd in six patients with SIADH (Group II) during both normo- and hypona tremia. As expected, in both groups, the serum uric acid concentration decreased during hyponatremia, but did so to a larger extent in the p atients with SIADH (-53% versus -29%, P < 0.02), Despite similar level s of hyponatremia (126 +/- 5 mmol/L and 125 +/- 5.5 mmol/L), of hypopr oteinemia (64 +/- 5 g/L and 63 +/- 5 g/L) and of salt excretion (FE(NA ), 0.66 +/- 0.28% and 0.73 +/- 0.25%), the urate clearance (8.3 +/- 3. 3 mL/min) and the fractional excretion of filtered uric acid (5.7 +/- 2%) in Group I were not significantly different during hyponatremia th an during normonatremia (6.4 +/- 1.5 mL/min and 5.4 +/- 0.9%). On the other hand, in Group II, both parameters were increased (17.8 +/- 2.9 mL/min and 19.6 +/- 5.3%; P < 0.001) and both values were higher than in the dDAVP-induced hyponatremia (P < 0.01). Additionally, the admini stration of a potent V-1-receptor agonist (triglycyl-lysine-vasopressi n) in a patient with central diabetes insipidus with preexisting dDAVP -induced hyponatremia produced a rapid increase of urate clearance. Be cause dDAVP acts only on the V-2 receptors, these data suggest that th e higher urate clearance observed during hyponatremia related to SIADH is not only the consequence of an increased ''effective vascular volu me,'' but that V-1-receptor stimulation also contributes to it, by a m echanism that remains to be determined.