Vol. 304, Issue 1, 156-161, January 2003

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

Mohamed H. Ahmed, Nick Ashton and Richard J. Balment

School of Biological Sciences, University of Manchester, Manchester, United Kingdom

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 kg¹ i.p.). After 3-h equilibration and a control hour, animals received either vehicle, chloroquine (0.04 mg h¹), N-nitro-L-arginine methyl ester (L-NAME) (nitric-oxide synthase inhibitor, 60 µg kg¹ h¹), 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.