Renal action of acute chloroquine and paracetamol administration in the anaesthetised, fluid-balanced rat

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University of Leeds (2002) J Physiol 544P, S106

Communications: Renal action of acute chloroquine and paracetamol administration in the anaesthetised, fluid-balanced rat

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

*Department of Physiology, University of Birmingham, Birmingham B15 2TT and †School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK

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Chloroquine, widely used in the treatment of malaria and rheumatoid arthritis, increases renal nitric oxide synthesis (Ahmed et al. 1999), which appears to mediate its diuretic action (Ahmed et al. 2000). We have also reported that acute chloroquine administration in rats treated with paracetamol for 30 days induced an antidiuresis which was associated with an increased plasma vasopressin concentration (Ahmed et al. 2001). In this study we examined the effect of acute co-administration of chloroquine and paracetamol on renal function.

Sprague-Dawley rats (n = 6 per group) were anaesthetised (Intraval 110 mg kg-1 I.P.) and prepared for I.V. infusion of dextrose (2.5 %). Following 4 h equilibration, animals received either vehicle, chloroquine (Chq, 0.04 mg h-1), paracetamol (Para, loading dose of 210 mg kg-1 followed by 110 mg kg-1 for 2 h) or combined chloroquine and paracetamol. Animals were humanely killed at the end of the experiment.

Chloroquine infusion alone was associated with a significant increase in urine flow rate (UFR) (Chq 5.6 ± 0.4 vs. vehicle 3.3 ± 0.2 ml h-1, means ± S.E.M., ANOVA, P < 0.05), glomerular filtration rate (GFR) (Chq 4.2 ± 0.5 vs. vehicle 2.5 ± 0.3 ml min-1, P < 0.05) and sodium excretion (Chq 124 ± 22 vs. vehicle 36 ± 2 mmol h-1, P < 0.05) while paracetamol alone reduced UFR (Para 2.0 ± 0.2 vs. vehicle 3.3 ± 0.2 ml h-1, P < 0.05), GFR (Para 1.7 ± 0.3 vs. vehicle 2.5 ± 0.3 ml min-1, P < 0.05) and sodium excretion (Para 12 ± 2 vs. vehicle 36 ± 2 mmol h-1, P < 0.05). Co-administration of paracetamol with chloroquine blocked the increases in UFR (Chq/Para 2.1 ± 0.2 vs. Chq 5.6 ± 0.4 ml h-1, P < 0.05), GFR (Para/Chq 2.9 ± 0.2 vs. Chq 4.2 ± 0.5 ml min-1, P < 0.05) and sodium excretion (Para/Chq 20 ± 5 vs. Chq 124 ± 22 mmol h-1, P < 0.05) observed with chloroquine alone.

Acute administration of paracetamol appeared to block the renal actions of chloroquine. These data conflict with our earlier observations in rats treated with paracetamol for 30 days prior to chloroquine infusion. In these animals UFR fell, GFR remained the same and sodium excretion increased. This suggests that paracetamol may modify the renal action of chloroquine by different mechanisms depending on the prior period of exposure to paracetamol.

All procedures accord with current UK legislation.

Where applicable, experiments conform with Society ethical requirements.

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