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Remifentanil preconditioning confers cardioprotection via the JAK/STAT but not PI3K/Akt pathway in rats
Author(s) -
Qiao Shigang,
Liu Yanan,
Wang Tingting,
Mao Xiaowen,
Wong Gordon T,
Xia Zhengyuan,
Irwin Michael G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1085.6
Subject(s) - cardioprotection , wortmannin , medicine , protein kinase b , pi3k/akt/mtor pathway , ischemic preconditioning , pharmacology , phosphorylation , endocrinology , anesthesia , ischemia , signal transduction , chemistry , biochemistry
The opioid receptor agonist remifentanil (REM) has been shown to attenuate myocardial ischemia reperfusion injury, but the underlying mechanism is unclear. We hypothesized that REM confers cardioprotection by activating the JAK/STAT and PI3K/Akt pathways, two important survival signal pathways for rescuing ischemic myocardium. After anesthesia, male Sprague‐Dawley rats were subjected to 30 min of coronary artery occlusion followed by 2 hours of reperfusion. Rats (n=5–6/group) were treated with vehicle, REM preconditioning (6 μg/kg, 3 consecutive 5 min intravenous REM interspersed with 5 min infusion‐free periods), or the GSK3β kinase inhibitor SB216763 (SB, 600 μg/kg) immediately prior to inducing ischemia in the absence or concomitant presence of the putative JAK2 inhibitor AG490 (3 mg/kg) or the PI3K inhibitor wortmannin (15 μg/kg). Myocardial infarct size (IS) was significantly reduced by either REM (25±10%) or SB (18±8%) compared to vehicle control (46±13%) (P<0.05). AG490 but not wortmannin abolished the IS sparing effect of REM, although AG490 or wortmannin alone did not significantly affect IS. REM enhanced myocardial phosphorylation of STAT3 and GSK3β compared with that of vehicle‐treated rats (P<0.05), and AG490 abolished these effects of REM. By contrast, REM reduced Akt phosphorylation. It is concluded that REM confers cardioprotection via the JAK/STAT but not the PI3K/Akt pathway. Supported by RGC/GRF grant (766709M to MGI) and NSFC grant (30872447 to ZX)