Pharmacologic stimulation of adenosine A2 receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers.
Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process.



Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A1 or A2 receptor agonists or antagonists were examined either in place of or against IPC.



The 7-day animal survival was significantly better in the IPC group than in the control group (87% vs 53%; n = 15, P < .05). The release of liver-related enzymes during reperfusion was suppressed better in the IPC group (P < .01). Recovery of adenosine triphosphate levels was faster in the IPC group (P < .01). After IPC, adenosine concentrations in liver tissue immediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained at that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A2 receptor agonist and opposed by adenosine A2 receptor antagonist.



The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A2 receptors.
Nakayama
H
H
Department of Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Japan.
Yamamoto
Y
Y
Kume
M
M
Yamagami
K
K
Yamamoto
H
H
Kimoto
S
S
Ishikawa
Y
Y
Ozaki
N
N
Shimahara
Y
Y
Yamaoka
Y
Y
D000222:Adaptation, Physiological; D000241:Adenosine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology
D020033:Protein Isoforms; D018047:Receptors, Purinergic P1; D000241:Adenosine