Arginine vasopressin mediates the chloroquine induced increase in renal sodium excretion

Abstract

SummaryWe 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 pg/min) for T h 20 min. We also monitored Na' excretion rates in Brattleboro AVP-deficient Di rats challenged with hypotonic saline load and administered chloroquine for I h 20 min. To establish whether chloroquine-induced changes in renal Na' excretion were mediated via AVP V, receptors, we studied Na' excretion rates in groups of SD rats administered chloroquine or AVP in the presence of AVP V, receptor antagonist 9.8 i 1.0 pmol/min to a peak of 14.1 f 0.9 pniol/rnin in SD rats ( n = 7 ) administered chloroquine. The Na' excretion rate remained unaltered around 8.5 pmol/min in rats simultaneously administered chloroquine and the AVP V, receptor antagonist. This compared with control rats ( 8 . 1 f 0.5 pmol/min, % = 7 ) and animals administered AVP V , receptor antagonist alone (8.7 f 0.6 p m o h i n , n=7). Chloroquine did not affect urine tlow, 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 V, receptors abolished the AVP-dependent increase in urinary Na' loss. We conclude that at least part of the chloroquine-induced increase in Na' excretion i s mediated by chloroquine stimulating an increase in plasma AVP concentration.The Na' excretion rate rose significantly (P<o.or) from a pretreatment level of keywords chloroquine, kidney toxicity, renal failure, malaria, sodium, aldosterone and arginine vasopressin correspondence Dr C.

Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

“…Chloroquine treatment either 3 h before or 6 h after CLP had a significant benefit on serum creatinine, BUN, and both cortical and OSOM histology scores. As chloroquine can have diuretic and natriuretic effects under normal conditions (3,36), it is not known whether these phenomena contribute to the protective effect of chloroquine on kidney function during sepsis; we also cannot rule out an effect of chloroquine on sepsis-associated hypotension. We used serum enzyme markers as surrogates for multiple organ damage, as well as examined splenic apoptosis and reduction of circulating bacteria as surrogates for immune paralysis to assess whether chloroquine simply decreased the overall severity of sepsis, or whether there was any selectivity toward the kidney.…”

The Effect of Chloroquine on Renal Function and Vasopressin Secretion: A Nitric Oxide-Dependent Effect

“…The natriuretic effect seemed to be mediated by vasopressin, via V 1 receptors (Musabayane et al, 1997), because chloroquine administration to Brattleboro, vasopressin-deficient rats had no effect on Na ϩ excretion (Musabayane et al, 1996). This chloroquine-induced natriuresis was not associated with a change in blood pressure or glomerular filtration rate (Musabayane et al, 1994) nor, surprisingly, urine flow rate, despite the concurrent increase in plasma vasopressin concentration.…”

“…We have previously reported that acute chloroquine administration in the anesthetized rat increased renal Na ϩ excretion and plasma arginine vasopressin concentration (Musabayane et al, 1994(Musabayane et al, , 1996. The natriuretic effect seemed to be mediated by vasopressin, via V 1 receptors (Musabayane et al, 1997), because chloroquine administration to Brattleboro, vasopressin-deficient rats had no effect on Na ϩ excretion (Musabayane et al, 1996).…”

“…To identify potentially subtle changes in renal function we have used a novel, servo-controlled fluid replacement system to match intravenous infusion rate to urinary excretion, thereby maintaining an euvolaemic state. This has an advantage over previous studies (Musabayane et al, 1993(Musabayane et al, , 1996 that used a constant infusion protocol that leads to extracellular volume expansion and compensatory changes in renal function that may mask some of the effects of chloroquine.…”

Renal Action of Acute Chloroquine and Paracetamol Administration in the Anesthetized, Fluid-Balanced Rat

“…We have previously suggested that chloroquine stimulates a diuresis in anesthetized, euvolemic rats by a combination of nitric oxide-induced cGMP generation and prostaglandin synthesis (Ahmed et al, 2003b). Together, these could act to inhibit the increase in medullary collecting duct cAMP generation that is expected to arise after a chloroquine-induced increase in plasma vasopressin concentration (Musabayane et al, 1996;Ahmed et al, 2003a). However, in the presence of paracetamol, a combination of higher circulating vasopressin levels (Ahmed et al, 2003b) and a predicted decreased in prostaglandin synthesis may allow sufficient cAMP generation to activate aquaporin 2 insertion and facilitate water reabsorption in the collecting duct.…”