Zusammenfassung
The adhesion of leukocytes to the endothelium of postcapillary venules
hallmarks a key event in ischemia-reperfusion injury. Adenosine has
been shown to protect from postischemic reperfusion injury, presumably
through inhibition of postischemic leukocyte-endothelial interaction.
This study was performed to investigate in vivo by which receptors
the effect of adenosine on postischemic leukocyte-endothelium interaction
is mediated. The hamster dorsal skinfold model and fluorescence microscopy
were used for intravital investigation of red cell velocity, vessel
diameter, and leukocyte-endothelium interaction in postcapillary
venules of a thin striated skin muscle. Leukocytes were stained in
vivo with acridine orange (0.5 mg kg-1 min-1 i.v.). Parameters were
assessed prior to induction of 4 h ischemia to the muscle tissue
and 0.5 h, 2 h, and 24 h after reperfusion. Adenosine, the adenosine
A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the
A2-selective agonist CGS 21,680, the non-selective adenosine receptor
antagonist xanthine amine congener (XAC), and the adenosine uptake
blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused via jugular
vein starting 15 min prior to release of ischemia until 0.5 h after
reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic
leukocyte-endothelium interaction 0.5 h after reperfusion (p less
than 0.01), while no inhibitory effect was observed with CCPA. Coadministration
of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI
alone effectively decreased postischemic leukocyte-endothelium interaction.
These findings indicate that adenosine reduces post-ischemic leukocyte-endothelium
interaction via A2 receptor and suggest a protective role of endogenous
adenosine during ischemia-reperfusion.
Nutzer