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This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.051037v1 306/2/478    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ahmed, M. H. Articles by Ashton, N. Search for Related Content PubMed PubMed Citation Articles by Ahmed, M. H. Articles by Ashton, N. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETAMINOPHEN CHLOROQUINE SODIUM

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

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

Chloroquine induces diuresis, natriuresis, and an increase in glomerular filtration rate (GFR) in the rat. These responses are modified in rats with analgesic nephropathy induced by long-term paracetamol (acetaminophen) administration. Here, the effects of acute paracetamol treatment on renal function and the response to chloroquine are reported. Under intraval anesthesia (100 mg kg^–1) male Sprague-Dawley rats (n = 6/group) were infused with 2.5% dextrose for 3 h. After a control hour, they received either vehicle, chloroquine (0.04 mg h^–1), paracetamol (priming dose of 210 mg kg^–1 followed by 110 mg kg^–1h^–1) or chloroquine and paracetamol over the next hour. Compared with vehicle, chloroquine infusion resulted in increases in GFR (2.4 ± 0.3 versus 4.8 ± 0.6 ml min^–1), urine flow (4.2 ± 0.3 versus 10.4 ± 0.7 ml h^–1), and sodium excretion (47.7 ± 4.1 versus 171.2 ± 18.6 µmol h^–1) and a reduction in urine osmolality (223.2 ± 5.9 versus 121.7 ± 23.9 mOsM kg^–1). Paracetamol reduced sodium excretion but had no effect on urine flow, GFR, or urine osmolality. When combined, paracetamol blocked the chloroquine-induced diuresis (3.9 ± 0.7 ml h^–1) and natriuresis (22.6 ± 8.5 µmol h^–1), attenuated the increase in glomerular filtration rate (3.5 ± 0.2 ml min^–1), and raised urine osmolality (280.0 ± 22.8 mOsM kg^–1). The differing effects of acute and long-term paracetamol treatment on basal and chloroquine-mediated renal function suggest that the length of prior exposure to paracetamol, and thus the presence of analgesic nephropathy, is an important determinant of the renal response to chloroquine.

Address correspondence to: Dr. Nick Ashton, School of Biological Sciences, University of Manchester, G38 Stopford Bldg., Oxford Rd., Manchester M13 9PT, UK. E-mail: nick.ashton{at}man.ac.uk