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

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 micromol 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 micromol 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.