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Sites of action of adenosine in interorgan preconditioning of the heart

Sites of action of adenosine in interorgan preconditioning of the heart Abstract The mechanism underlying interorgan preconditioning of the heart remains elusive, although a role for adenosine and activation of a neurogenic pathway has been postulated. We tested in rats the hypothesis that adenosine released by the remote ischemic organ stimulates local afferent nerves, which leads to activation of myocardial adenosine receptors. Preconditioning with a 15-min mesenteric artery occlusion (MAO15) reduced infarct size produced by a 60-min coronary artery occlusion (60-min CAO) from 68 ± 2% to 48 ± 4% ( P < 0.05). Pretreatment with the ganglion blocker hexamethonium or 8-( p -sulfophenyl)theophylline (8-SPT) abolished the protection by MAO15. Intramesenteric artery (but not intraportal vein) infusion of adenosine (10 μg/min) was as cardioprotective as MAO15, which was also abolished by hexamethonium. Whereas administration of hexamethonium at 5 min of reperfusion following MAO15 had no effect, 8-SPT at 5 min of reperfusion abolished the protection. Permanent reocclusion of the mesenteric artery before the 60-min CAO enhanced the cardioprotection by MAO15 (30 ± 5%), but all protection was abolished when 8-SPT was administered after reocclusion of the mesenteric artery. Together, these findings demonstrate the involvement of myocardial adenosine receptors. We therefore conclude that locally released adenosine during small intestinal ischemia stimulates afferent nerves in the mesenteric bed during early reperfusion, initiating a neurogenic pathway that leads to activation of myocardial adenosine receptors. adenosine receptors myocardial infarction neurogenic pathway remote myocardial preconditioning preconditioning at a distance small intestine Footnotes Address for reprint requests and other correspondence: D. J. Duncker, Experimental Cardiology, Thoraxcenter, Erasmus Univ. Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands (E-mail: [email protected] ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. First published February 21, 2002;10.1152/ajpheart.01031.2001 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

Sites of action of adenosine in interorgan preconditioning of the heart

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.01031.2001
pmid
12063271
Publisher site
See Article on Publisher Site

Abstract

Abstract The mechanism underlying interorgan preconditioning of the heart remains elusive, although a role for adenosine and activation of a neurogenic pathway has been postulated. We tested in rats the hypothesis that adenosine released by the remote ischemic organ stimulates local afferent nerves, which leads to activation of myocardial adenosine receptors. Preconditioning with a 15-min mesenteric artery occlusion (MAO15) reduced infarct size produced by a 60-min coronary artery occlusion (60-min CAO) from 68 ± 2% to 48 ± 4% ( P < 0.05). Pretreatment with the ganglion blocker hexamethonium or 8-( p -sulfophenyl)theophylline (8-SPT) abolished the protection by MAO15. Intramesenteric artery (but not intraportal vein) infusion of adenosine (10 μg/min) was as cardioprotective as MAO15, which was also abolished by hexamethonium. Whereas administration of hexamethonium at 5 min of reperfusion following MAO15 had no effect, 8-SPT at 5 min of reperfusion abolished the protection. Permanent reocclusion of the mesenteric artery before the 60-min CAO enhanced the cardioprotection by MAO15 (30 ± 5%), but all protection was abolished when 8-SPT was administered after reocclusion of the mesenteric artery. Together, these findings demonstrate the involvement of myocardial adenosine receptors. We therefore conclude that locally released adenosine during small intestinal ischemia stimulates afferent nerves in the mesenteric bed during early reperfusion, initiating a neurogenic pathway that leads to activation of myocardial adenosine receptors. adenosine receptors myocardial infarction neurogenic pathway remote myocardial preconditioning preconditioning at a distance small intestine Footnotes Address for reprint requests and other correspondence: D. J. Duncker, Experimental Cardiology, Thoraxcenter, Erasmus Univ. Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands (E-mail: [email protected] ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. First published February 21, 2002;10.1152/ajpheart.01031.2001 Copyright © 2002 the American Physiological Society

Journal

AJP - Heart and Circulatory Physiology – The American Physiological Society

Published: Jul 1, 2002

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