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.
School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK.
Mohamed H
MH
Ahmed
Richard J
RJ
Balment
Nick
N
Ashton
D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D014554:Urination / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D002738:Chloroquine; D012964:Sodium