期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 36, 期 3, 页码 411-421出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2003.12.008
关键词
bradykinin; NECA; nitric oxide; PI3 kinase; reperfusion injury
资金
- NHLBI NIH HHS [HL-50688, HL-20648] Funding Source: Medline
The adenosine A(1)/A(2) adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) and bradykinin both limit infarction when administered at reperfusion in rabbits. This study compares the signal transduction pathways responsible for their anti-infarct effect. Receptor agonists were administered to isolated rabbit hearts starting 25 min after the onset of a 30-min period of ischemia and continued into the 2-h reperfusion period. Infarct size was measured. Both NECA and bradykinin decreased infarction from 31.5 +/- 2.4% of the risk zone in untreated hearts to 11.8 +/- 2.0% and 15.4 +/- 2.4%, respectively (P < 0.05). Protection from both agents was blocked by PD98059, wortmannin, and N-omega-nitro-L-arginine methyl ester (L-NAME), thus demonstrating dependence on activation of extracellular regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) and stimulation of nitric oxide synthase (NOS). Both wortmannin and PD98059 prevented phosphorylation of ERK 1/2 in NECA-treated hearts, whereas only wortmannin and not PD98059 blocked Akt phosphorylation. These data suggest Akt is upstream of ERK 1/2. In addition, 8-(3-chlorostyryl) caffeine blocked NECAs protection indicating that A(2) adenosine receptors trigger NECA's anti-infarct effect. Of note, both bradykinin and acetylcholine (ACh) administered before ischemia to trigger preconditioning's cardioprotection use PI3K and NOS in their signaling pathway. Curiously, however, ACh, unlike bradykinin, was not protective when administered at reperfusion. Hence, both NECA and bradykinin administered at reperfusion protect through a common signaling pathway that includes PI3K, NO, and ERK. (C) 2003 Elsevier Ltd. All rights reserved.
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