Abstract

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.