The effect of chloroquine on renal function and vasopressin secretion: a nitric oxide-dependent effect.
We have previously reported that chloroquine administration increases plasma vasopressin concentration and urinary sodium excretion in Sprague-Dawley rats. Because chloroquine has also been shown to stimulate nitric oxide production, the aim of this study was to determine whether nitric oxide mediates chloroquine-induced changes in renal function and secretion of vasopressin. Sprague-Dawley rats (n = 6-8/group) were infused with 2.5% dextrose under Intraval anesthesia (100 mg kg(-1) i.p.). After 3-h equilibration and a control hour, animals received either vehicle, chloroquine (0.04 mg h(-1)), N(omega)-nitro-L-arginine methyl ester (L-NAME) (nitric-oxide synthase inhibitor, 60 microg kg(-1) h(-1)), or combined chloroquine and L-NAME over the next hour. L-NAME or vehicle infusion continued for a further recovery hour. Plasma was collected from a parallel group of animals for vasopressin radioimmunoassay. Chloroquine stimulated a significant increase (p < 0.05) in urine flow rate, glomerular filtration rate, and sodium excretion over the hour of infusion, in comparison with vehicle-infused rats. These effects continued after cessation of chloroquine, reaching maxima in the following recovery hour. Coadministration of L-NAME abolished these effects, returning all parameters to levels comparable with those in vehicle-infused animals. Chloroquine administration was accompanied by a significant increase (p < 0.05) in plasma vasopressin, which was also reversed by L-NAME. The effects of chloroquine on renal function and vasopressin secretion seem to be mediated by pathways involving nitric oxide. These data suggest that chloroquine may stimulate nitric-oxide synthase both centrally, stimulating vasopressin secretion, and within the kidney, where it modulates glomerular hemodynamics and tubular function.
Ahmed
Mohamed H
MH
School of Biological Sciences, University of Manchester, Manchester, United Kingdom. nick.ashton@man.ac.uk
Ashton
Nick
N
Balment
Richard J
RJ
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001826:Body Fluids / Q000502:physiology; D002738:Chloroquine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
D000962:Antimalarials; D004791:Enzyme Inhibitors; D014667:Vasopressins; D009569:Nitric Oxide; D002738:Chloroquine; D012964:Sodium; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester