Adenosine a2-receptor activation inhibits neutrophil-mediated
injury to coronary endothelium by attenuating superoxide radical
generation and adherence.
Zhao, Zhi-Qing, Hiroki Sato, Mark W. Williams, Adolfo Z. Fernandez,
Jakob Vinten-Johansen.
Department of Cardiothoracic Surgery, Bowman Gray School of
Medicine of Wake Forest University, Winston-Salem, North Carolina
27157-1906
APStracts 3:0100H, 1996.
Adenosine (ADO) attenuates neutrophil (PMN)-mediated damage, partly by
inhibiting superoxide anion (-O) generation and PMN adherence to the
coronary artery endothelium. This study tests the hypothesis that the
antineutrophil effects of ADO are mediated by A2-receptor activation.
Isolated canine PMNs were activated by 100 nM platelet activating
factor (PAF). Compared to untreated activated PMN (100%), ADO
attenuated -O production (46 +/- 9% of activated PMN), which was
mimicked by the A2-agonist CGS-21680 (50 +/- 6% of activated PMN),
unaltered by selective A1-antagonism with KW-3902 in the presence of
ADO (40 +/- 7%), but blocked by combined A1-A2 blockade with 8-p
-sulfophenyl theophylline (SPT, 94 +/- 14%). ADO reduced adherence of
fluorescent PMN to endothelial surfaces of isolated canine coronary
artery segments from 174 +/- 12/mm2 to 29 +/- 9/mm2 (p<0.01),
which was unaltered by A1-antagonism (35 +/- 7/mm2), but was reversed
by SPT (150 +/- 11/mm2). CGS-21680 inhibited adherence (48 +/- 8/mm2)
comparable with that of ADO. Canine coronary artery rings were
incubated with activated PMN to induce injury to the endothelium. The
EC50 (-log M) derived from dose-relaxation responses to acetylcholine
in PMN-damaged rings was significantly (p<0.05) less in ADO
(6.88 +/- 0.08) and CGS-treated (7.12 +/- 0.09) rings than untreated
rings (6.54 +/- 0.10). This protection with ADO was reversed by
inclusion of SPT (6.49 +/- 0.12) but not KW-3902 (6.96 +/- 0.07). We
conclude that ADO reduces PMN-induced coronary endothelial injury by
A2-receptor mediated inhibition of -O generation and adherence.
Received 27 December 1994; accepted in final form 28 February
1996.
APS Manuscript Number H1137-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96