Arginine vasopressin mediates the chloroquine induced increase in renal sodium excretion
Abstract: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 mug/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-cyclopentame thylenepropionic 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.
Document Type: Research Article
Affiliations: 1: School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK 2: Department of Obstetrics and Gynaecology, United Medical and Dental Schools, St Thomas Campus, Lambeth Palace, London SE1 7EH, UK
Publication date: August 1, 1996