Arginine vasopressin mediates the chloroquine induced increase in renal sodium excretion.

We postulated that chloroquine increases plasma arginine vasopressin (AVP) concentrations thus altering renal Na+ clearance. Therefore, we studied a relationship between plasma AVP concentrations and urinary Na+ output in separate groups of Sprague-Dawley (SD) rats administered chloroquine (3 micrograms/min) for 1 h 20 min. We also monitored Na+ excretion rates in Brattleboro AVP-deficient Di rats challenged with hypotonic saline load and administered chloroquine for 1 h 20 min. To establish whether chloroquine-induced changes in renal Na+ excretion were mediated via AVP V1 receptors, we studied Na+ excretion rates in groups of SD rats administered chloroquine or AVP in the presence of AVP V1 receptor antagonist (1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-2-O-methyltyrosine arginine vasopressin (d(CH2)5(Tyr(Me)2) AVP) at 11 pmol/min for 1 h 20 min. The Na+ excretion rate rose significantly (P < 0.01) from a pretreatment level of 9.8 +/- 1.0 mumol/min to a peak of 14.1 +/- 0.9 mumol/min in SD rats (n = 7) administered chloroquine. The Na+ excretion rate remained unaltered around 8.5 mumol/min in rats simultaneously administered chloroquine and the AVP V1 receptor antagonist. This compared with control rats (8.1 +/- 0.5 mumol/min, n = 7) and animals administered AVP V1 receptor antagonist alone (8.7 +/- 0.6 mumol/min, n = 7). Chloroquine did not affect urine flow, Na+ or K+ excretion rates in Brattleboro AVP-deficient Di rats. Administration of AVP alone was associated with significant increases in renal Na+ excretion rate. Blockade of AVP V1 receptors abolished the AVP-dependent increase in urinary Na+ loss. We conclude that at least part of the chloroquine-induced increase in Na+ excretion is mediated by chloroquine stimulating an increase in plasma AVP concentration.