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 ω-nitro-l-arginine methyl ester (l-NAME) (nitric-oxide synthase inhibitor, 60 μg kg−1 h−1), or combined chloroquine andl-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 ofl-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.