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Background: Renal interstitial inflammation is a consequence of unilateral ureteral obstruction (UUO). Following ischemia/reperfusion, adenosine reduces renal inflammation and injury, effects which are potentiated by type 4 phosphodiesterase inhibitors. We therefore studied the effects of A2A adenosine receptor agonist (ATL146e), and PDE4 inhibitor (rolipram) in mice subjected to UUO. Methods: Mice were subjected to UUO or sham operation, and received either vehicle or ATL146e + rolipram by osmotic minipump for 1 or 7 days. At 1, 3, 7, or 14 days after operation, renal macrophage infiltration, apoptosis, proliferation, tubular atrophy, and interstitial fibrosis were quantitated, and expressions of IL-6 and TGF-β mRNA were determined. Results: ATL146e + rolipram reduced macrophage infiltration by 40% after 3 days UUO (p < 0.05). Tubular apoptosis, tubular atrophy, and interstitial fibrosis were increased by 7 or 14 days UUO, but were unaffected by ATL146e + rolipram. However, cellular proliferation was increased by ATL146e + rolipram in the obstructed kidney. ATL146e + rolipram had no effect on the renal expression of IL-6 and TGF-β mRNA. Conclusions: A2A receptor activation and PDE4 inhibition transiently reduce renal macrophage infiltration, but do not ameliorate the renal response to UUO. We speculate that the persistent stimulus for inflammation triggered by UUO cannot be reversed by agents that suppress inflammatory cell activation alone. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Investigates the effect of A[sub 2A] adenosine receptors (A[sub 2A]AR) activation on protection of the liver from ischemia-reperfusion (I/R) injury and determines whether suppression of hepatic inflammatory chemokine production plays a role in this protection. Demonstration that the selective agonist of the A[sub 2a]AR produces a protection of wild-type C57BL/6 mice from liver I/R injury that is absent in congenic animals lacking the A[sub 2A]AR gene.

Presents information on a study which examined the effect of selective activation of A... adenosine receptors on ischemia-reperfusion injury in rat kidney. Methods of the study; Results and discussion.

Activation of A[sub2A] adenosine receptors (A[sub2A]Rs) protects kidneys from ischemia-reperfusion injury (IRI). A[sub2A]Rs are expressed on bone marrow-derived (BM-derived) cells and renal smooth muscle, epithelial, and endothelial cells. To measure the contribution of A[sub2A]Rs on BM-derived cells in suppressing renal IRI, we examined the effects of a selective agonist of A[sub2A]Rs, ATL146e, in chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A[sub2A]R-KO, or WT mice to produce GFP → WT, A[sub2A]-KO → WT, or WT → WT mouse chimera. We found little or no repopulation of renal vascular endothelial cells by donor BM with or without renal IRI. ATL146e had no effect on IRI in A[sub2A]-KO mice or A[sub2A]-KO → WT chimera, but reduced the rise in plasma creatinine from IRI by 75% in WT mice and by 60% in WT → WT chimera. ATL146e reduced the induction of IL-6, IL-β, IL-1ra, and TGF-α mRNA in WT → WT mice but not in A[sub2A]-KO → WT mice. Plasma creatinine was significantly greater in A[sub2A]-KO than in WT mice after IRI, suggesting some renal protection by endogenous adenosine. We conclude that protection from renal IRI by A[sub2A]R agonists or endogenous adenosine requires activation of receptors expressed on BM-derived cells. [ABSTRACT FROM AUTHOR]