Abstract:
OBJECTIVES:To characterize the 'anti-ischemic' effects of adenosine metabolism inhibition in ischemic-reperfused myocardium. METHODS:Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 microM erythro-2-(2-hydroxy-3-nonyl)adenine; EHNA) adenosine kinase inhibition (10 microM iodotubercidin; IODO), or 10 microM adenosine. Hearts overexpressing A(1) adenosine receptors (A(1)ARs) were also studied. RESULTS:EHNA treatment reduced ischemic contracture and post-ischemic diastolic pressure (14+/-2 vs. 20+/-1 mmHg), increased recovery of developed pressure (66+/-3 vs. 53+/-2%) and reduced LDH efflux (8.9+/-1.6 vs. 18.0+/-1.7 I.U./g). IODO also improved functional recovery (to 60+/-2%) and reduced LDH efflux (5.3+/-1.7 I.U./g), as did treatment with 10 microM adenosine. Protection with EHNA was reversed by co-infusion of IODO or 50 microM 8-rho-sulfophenyltheophylline (adenosine receptor antagonist), but unaltered by 20 microM inosine+10 microm hypoxanthine. Similarly, effects of iodotubercidin were inhibited by EHNA and 8-rho-sulfophenyltheophylline. A(1)AR overexpression exerted similar effects to EHNA and EHNA or IODO alone enhanced recovery while EHNA+IODO reduced recovery in transgenic hearts. Functional recoveries and xanthine oxidase reactant levels were unrelated in the groups studied. CONCLUSIONS:Adenosine deaminase or kinase inhibition protects from ischemia-reperfusion. Cardioprotection via these enzyme inhibitors requires a functioning purine salvage pathway and involves enhanced adenosine receptor activation. Reduced formation of inosine is unimportant in EHNA-mediated protection.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Peart J,Matherne GP,Cerniway RJ,Headrick JPdoi
10.1016/s0008-6363(01)00360-1subject
Has Abstractpub_date
2001-10-01 00:00:00pages
120-9issue
1eissn
0008-6363issn
1755-3245pii
S0008636301003601journal_volume
52pub_type
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更新日期:1995-03-01 00:00:00
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更新日期:2017-03-01 00:00:00
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更新日期:2007-09-01 00:00:00
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更新日期:2009-07-15 00:00:00
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更新日期:2000-06-01 00:00:00
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更新日期:1999-03-01 00:00:00
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更新日期:1979-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-12-01 00:00:00
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更新日期:2019-03-15 00:00:00