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Am J Physiol Renal Physiol 258: F1554-F1560, 1990;
0363-6127/90 $5.00
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AJP - Renal Physiology, Vol 258, Issue 6 1554-F1560, Copyright © 1990 by American Physiological Society


ARTICLES

The role of adenosine in HgCl2-induced acute renal failure in rats

N. Rossi, V. Ellis, T. Kontry, S. Gunther, P. Churchill and A. Bidani
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.

It has been proposed that adenosine mediates the renal hemodynamic changes in acute renal failure (ARF) and that these changes are pathogenic in reducing glomerular filtration rate. Consistently, adenosine-receptor antagonists such as theophylline have been shown to have protective effects in several experimental models of ARF. The present experiments were designed to explore the potential role of adenosine in HgCl2-induced ARF in rats. In isolated perfused rat kidneys, HgCl2 increased adenosine production and induced a concentration-dependent vasoconstriction. However, the vasoconstriction was unrelated to adenosine production and was not antagonized by theophylline. During the initiation phase of HgCl2-induced ARF in intact rats (first 4 h after injection), theophylline failed to reverse the reduction in inulin clearance, and this failure could not be attributed to a loss of vascular responsiveness to adenosine, since N6-cyclohexyladenosine, a receptor agonist, produced a further reduction in inulin clearance. Furthermore, theophylline actually had deleterious effects during the maintenance phase of HgCl2-induced ARF in intact unanesthetized rats, as evidenced by higher mean serum creatinine values in theophylline-injected rather than in saline-injected rats, on both the second and third days after HgCl2 injection. Therefore HgCl2 acutely increases renal adenosine production, but increased adenosine does not mediate acute HgCl2-induced renal vasoconstriction, and adenosine-receptor antagonism does not have protective effects during the initiation or the maintenance phases of HgCl2-induced ARF in rats. These results provide no support for the hypothesis that increased adenosine mediates the hemodynamic changes in HgCl2-induced ARF.


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H. T. Lee and C. W. Emala
Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A1 and A3 receptors
Am J Physiol Renal Physiol, March 1, 2000; 278(3): F380 - F387.
[Abstract] [Full Text] [PDF]




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