Further characterization of the protective effect of 8-cyclopentyl-1,3-dipropylxanthine on glycerol-induced acute renal failure in the rat.
In the rat, treatment with the alkylxanthine 8-cyclopentyl-1,3-dipropylxanthine (CPX) at a dose of 0.1 mg kg-1 antagonizes adenosine-induced falls in renal blood flow and reduces the severity of glycerol-induced acute renal failure. Treatment of glycerol-injected rats with 0.03 mg kg-1 of CPX resulted in no significant improvements in a range of indices of renal function. However, treatment with 0.1 or 0.3 mg kg-1 doses of CPX did significantly ameliorate acute renal failure although there were no significant differences in the degree of protection of renal function afforded by these two doses. In glycerol-injected rats, 0.1 or 0.3 mg kg-1 CPX administered either as a single dose or repeated doses every 12 h for two days did not inhibit renal phosphodiesterase. Thus the beneficial effects of CPX can be produced by doses that have no effect on renal phosphodiesterase activity whereas 0.1 mg kg-1 of CPX has been shown previously to antagonize the actions of adenosine. The findings provide further evidence that the beneficial effect of CPX in glycerol-induced acute renal failure is a consequence of adenosine antagonism and not phosphodiesterase inhibition.
Panjehshahin
M R
MR
Department of Pharmacology, University of Leeds, UK.
Munsey
T S
TS
Collis
M G
MG
Bowmer
C J
CJ
Yates
M S
MS
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D003404:Creatinine / Q000097:blood; D005990:Glycerol / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014508:Urea / Q000097:blood
C053907:8-cyclopentyl-1,3-dimethylxanthine; D014508:Urea; D003404:Creatinine; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine; D005990:Glycerol