title: 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 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.
authors.affiliation: School of Medicine, University of Zimbabwe, Harare, Zimbabwe.
authors.forename: C T
authors.initials: CT
authors.lastname: Musabayane
authors.forename: R J
authors.initials: RJ
authors.lastname: Windle
authors.forename: M L
authors.initials: ML
authors.lastname: Forsling
authors.forename: R J
authors.initials: RJ
authors.lastname: Balment
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood / Q000172:deficiency / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000187:drug effects*; D012964:Sodium / Q000652:urine*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000450:Aldosterone; D002738:Chloroquine; D012964:Sodium; D011188:Potassium