Renal function in a rat model of analgesic nephropathy: effect of chloroquine.
The antimalaria drug chloroquine is often taken against a background of analgesic nephropathy caused by nonsteroidal anti-inflammatory drugs such as paracetamol (acetaminophen). Chloroquine has marked effects on the normal kidney and stimulates an increase in plasma vasopressin via nitric oxide. The aim of this study was to determine the renal action of chloroquine in a model of analgesic nephropathy. Sprague-Dawley rats (n = 6-8/group) were treated with paracetamol (500 mg kg(-1) day(-1)) for 30 days in drinking water to induce analgesic nephropathy; control rats received normal tap water. Under intraval anesthesia (100 mg kg(-1)) rats were infused with 2.5% dextrose for 3 h to equilibrate and after a control hour they received either vehicle, chloroquine (0.04 mg h(-1)), N(omega)-nitro-L-arginine methyl ester (L-NAME, nitric-oxide synthase inhibitor, 60 micro g kg(-1) h(-1)) or combined chloroquine and L-NAME over the next hour. Plasma was collected from a parallel group of animals for vasopressin radioimmunoassay. Long-term paracetamol treatment resulted in a decrease in glomerular filtration rate (p < 0.05), sodium excretion (p < 0.001), and urine osmolality (p < 0.001), but no change in urine flow rate compared with untreated animals. Chloroquine administration in paracetamol treated rats induced a significant reduction (p < 0.05) in urine flow rate and a significant increase in plasma vasopressin (p < 0.001). These effects were blocked by coadministration of L-NAME and thus seem to be mediated by a pathway involving nitric oxide. However, these responses contrast with the chloroquine-induced diuresis previously observed in untreated rats, possibly reflecting paracetamol inhibition of renal prostaglandin synthesis and consequent moderation of vasopressin's action.
Ahmed
Mohamed H
MH
School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Ashton
Nick
N
Balment
Richard J
RJ
D000082:Acetaminophen / Q000494:pharmacology; D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007671:Kidney Concentrating Ability; D007674:Kidney Diseases / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D014554:Urination / Q000187:drug effects*; D014667:Vasopressins / Q000097:blood
D018712:Analgesics, Non-Narcotic; D014667:Vasopressins; D000082:Acetaminophen; D002738:Chloroquine; D012964:Sodium