AIMS: Adenosine is involved in classic pre-conditioning (PC) in most species, acting through especially adenosine A1 and A3 receptors. We studied whether the adenosine A1 receptor (A1R) was important for remote, delayed adaptation to ischaemia using a mouse with targeted deletion of the A1R gene. METHODS: Remote, delayed adaptation was evoked by brain ischaemia (BIPC) through bilateral ligation of the internal carotid arteries. Through microdialysis probes placed in the brain and the abdominal aorta, we found that plasma adenosine increased following carotid artery ligation. Twenty-four hours after ligation, hearts were isolated, Langendorff perfused and subjected to 40 min global ischaemia and 60 min reperfusion. Hearts from sham operated and BIPC animals either with (A1R+/+) or without (A1R-/-) the gene for the adenosine A(1)R were compared with each other. RESULTS: In wild types, BIPC reduced infarct size and improved functional recovery during reperfusion, but BIPC did not protect hearts of A1R-/- mice. There were no significant differences between sham-operated A1R+/+ and A1R-/- in recovery of function or infarct size. The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) were phosphorylated during reperfusion of sham treated hearts. The increase in ERK1/2 and p38 phosphorylation detected was attenuated in hearts of BIPC or A1R-/- animals. CONCLUSION: During BIPC adenosine acting on the A1R appears necessary for myocardial protection. MAPK signalling may possibly be involved in organ protection during the delayed phase of remote, delayed adaptation. Copyright 2004 Scandinavian Physiological Society
AIMS: Adenosine is involved in classic pre-conditioning (PC) in most species, acting through especially adenosine A1 and A3 receptors. We studied whether the adenosine A1 receptor (A1R) was important for remote, delayed adaptation to ischaemia using a mouse with targeted deletion of the A1R gene. METHODS: Remote, delayed adaptation was evoked by brain ischaemia (BIPC) through bilateral ligation of the internal carotid arteries. Through microdialysis probes placed in the brain and the abdominal aorta, we found that plasma adenosine increased following carotid artery ligation. Twenty-four hours after ligation, hearts were isolated, Langendorff perfused and subjected to 40 min global ischaemia and 60 min reperfusion. Hearts from sham operated and BIPC animals either with (A1R+/+) or without (A1R-/-) the gene for the adenosine A(1)R were compared with each other. RESULTS: In wild types, BIPC reduced infarct size and improved functional recovery during reperfusion, but BIPC did not protect hearts of A1R-/- mice. There were no significant differences between sham-operated A1R+/+ and A1R-/- in recovery of function or infarct size. The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) were phosphorylated during reperfusion of sham treated hearts. The increase in ERK1/2 and p38 phosphorylation detected was attenuated in hearts of BIPC or A1R-/- animals. CONCLUSION: During BIPC adenosine acting on the A1R appears necessary for myocardial protection. MAPK signalling may possibly be involved in organ protection during the delayed phase of remote, delayed adaptation. Copyright 2004 Scandinavian Physiological Society
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