Activation of A 3 adenosine receptors attenuates lung injury after in vivo reperfusion

Julia Rivo, Evelyne Zeira, Eithan Galun, Idit Matot

Research output: Contribution to journalArticlepeer-review

Abstract

Background: A 3 adenosine receptor (AR) activation worsens or protects against renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the current study were to examine in an in vivo model the effect of A 3AR activation on IR lung injury and investigate the mechanism by which it exerts its effect. Methods: The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A 3 receptor agonist IB-MECA (300 μg/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A 3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor N w-nitro-L- arginine benzyl ester. Results: IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 ± 4%; IB-MECA, 18 ± 2%), wet:dry weight ratio (IR, 8.2 ± 0.4; IB-MECA, 4 ± 2), and myeloperoxidase activity (IR, 0.52 ± 0.06 U/g; IB-MECA, 0.17 ± 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A 3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor N wnitro-L-arginine benzyl ester. Conclusions: In the feline lung, the A 3AR agonist IB-MECA confers a powerful protection against IR lung injury. This effect is mediated by a nitric oxide synthase-independent pathway and involves opening of adenosine triphosphate-sensitive potassium channels. Therefore, selective activation of A 3AR may be an effective means of protecting the reperfused lung.

Original languageEnglish
Pages (from-to)1153-1159
Number of pages7
JournalAnesthesiology
Volume101
Issue number5
DOIs
StatePublished - Nov 2004
Externally publishedYes

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