The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats.
Several previous observations support the hypothesis that increased adenosine production and release mediate, at least in part, the reductions in renal blood flow and glomerular filtration rate in ischemic acute renal failure (ARF). If this hypothesis is correct, dipyridamole should potentiate these changes, since it blocks cellular adenosine uptake, thereby increasing the concentration and potentiating the effects of extracellular adenosine. Moreover, theophylline should block the effects of dipyridamole, since it is an adenosine receptor antagonist. These predictions were tested in three groups of anesthetized rats. All rats were subjected to 30 min of left renal artery occlusion; 30 min after relieving the occlusion, a 45-min clearance period was begun. The control group was given saline i.v.; the two experimental groups received either dipyridamole (24 micrograms X min-1 X kg-1) or dipyridamole plus theophylline i.v. (111 mumol/kg as a prime, 1.1 mumol X min-1 X kg-1 as an infusion). In the control group, the previously ischemic left kidneys exhibited decreased clearances of para-aminohippurate and inulin (CPAH and CIn), filtration fraction (FF), and urine/plasma inulin concentration (U/PIn), and increased urine flow (V), Na excretion (UNaV), and fractional Na excretion (FENa) in comparison with the contralateral right kidney. Dipyridamole pretreatment did not affect the right kidney, but it intensified the reductions in left kidney CPAH, CIn, and FF. Theophylline blocked all these effects of dipyridamole on the left kidney, and increased renal plasma flow (CPAH/PAH extraction), despite a decrease in systemic arterial blood pressure. These results are further support for the hypothesis that adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.
Lin
J J
JJ
Wayne State University School of Medicine, Detroit, MI 48201.
Churchill
P C
PC
Bidani
A K
AK
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000652:urine
D004176:Dipyridamole; D012964:Sodium