Sites of action of adenosine in interorgan preconditioning of the heart.
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 microg/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.
Liem
David A
DA
Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands.
Verdouw
Pieter D
PD
Ploeg
Harald
H
Kazim
Shahla
S
Duncker
Dirk J
DJ
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003331:Coronary Vessels / Q000503:physiopathology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D018738:Hexamethonium / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000098:blood supply / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D008643:Mesentery / Q000294:innervation / Q000503:physiopathology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011169:Portal Vein / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D005730:Ganglionic Blockers; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018738:Hexamethonium; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine