REDUCTION OF POSTISCHEMIC LEUKOCYTE-ENDOTHELIUM INTERACTION BY ADENOSINE VIA A2-RECEPTOR

被引:44
作者
NOLTE, D [1 ]
LORENZEN, A [1 ]
LEHR, HA [1 ]
ZIMMER, FJ [1 ]
KLOTZ, KN [1 ]
MESSMER, K [1 ]
机构
[1] UNIV HEIDELBERG, INST PHARMACOL, W-6900 HEIDELBERG, GERMANY
关键词
ADENOSINE RECEPTORS; ISCHEMIA REPERFUSION; LEUKOCYTE ENDOTHELIUM INTERACTION; MICROCIRCULATION;
D O I
10.1007/BF00165307
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 iv.). 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<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 postischemic leukocyte-endothelium interaction via A2 receptor and suggest a protective role of endogenous adenosine during ischemia-reperfusion.
引用
收藏
页码:234 / 237
页数:4
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