Hypercholesterolemia Abrogates Sevoflurane-Induced Delayed Preconditioning Against Myocardial Infarct in Rats by Alteration of Nitric Oxide Synthase Signaling
Hypercholesterolemia Abrogates Sevoflurane-Induced Delayed Preconditioning Against Myocardial Infarct in Rats by Alteration of Nitric Oxide Synthase Signaling
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高胆固醇血症通过改变一氧化氮合酶信号传导消除七氟烷诱导的大鼠心肌梗塞延迟预处理
DOI：
10.1097/shk.0b013e318249b7b6
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发表时间：
2012
期刊：
影响因子：
3.1
通讯作者：
Min Yan
中科院分区：
文献类型：
--
作者：
Feng;Lei;Wen;Ling;Mei;Jing Yu;Gang Chen;Lina Yu;Min Yan
ABSTRACT The aim of the current study was to determine whether hypercholesterolemia affects the delayed sevoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury and, if so, the underlying mechanism. Male Sprague-Dawley rats fed 2% cholesterol-enriched chow for 8 weeks were subjected to sevoflurane preconditioning (2.4% vol/vol, 1 h) 24 h before myocardial ischemia was induced by occluding the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The hemodynamic parameters left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rise/fall rate of left ventricular pressure were continuously monitored, and myocardial infarct size was determined at the end of reperfusion. The protein expression of myocardial nitric oxide synthase (NOS), Bcl-2, and Bad was assessed before ischemia. We found that the left ventricular hemodynamic parameters during the whole IR procedure and the myocardial infarct size did not significantly differ between the normocholesterolemic and hypercholesterolemic control groups. The hemodynamic parameters were all markedly improved during the reperfusion period, and the myocardial infarct size was significantly reduced by delayed sevoflurane preconditioning in normocholesterolemic rats, but all of these improvements were reversed by N-(3-(aminomethyl)benzyl) acetamidine (1400W, 1 mg/kg; i.v., 10 min before ischemia), a selective inducible NOS (iNOS) inhibitor, and 5-hydroxy decanoate sodium (5 mg/kg, i.v., 10 min before ischemia), a mitochondrial ATP-dependent K+ channel blocker. Such cardiac improvement induced by delayed sevoflurane preconditioning did not occur in hypercholesterolemic rats and was not exacerbated by 1400W or 5-hydroxy decanoate sodium. The expression of myocardial iNOS was markedly enhanced by delayed sevoflurane preconditioning in normocholesterolemic, but not in hypercholesterolemic rats. The expression of endothelial NOS and Bad did not differ among all groups. The expression of myocardial phosphorylated endothelial NOS, Bcl-2, and phosphorylated Bad in normocholesterolemic rats was not affected by delayed sevoflurane preconditioning but was decreased in the hypercholesterolemic control group, and this was not reversed by sevoflurane, compared with the normocholesterolemic control group. Taken together, these results indicate that sevoflurane preconditioning exerts delayed cardioprotection against IR injury in normocholesterolemic rats, which is blocked by hypercholesterolemia potentially via interference with the iNOS/mitochondrial ATP-dependent K+ channel pathway.
DOI：
10.1152/ajpheart.00707.2002
发表时间：
2003
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
C. Steenbergen;C. Afshari;J. Petranka;J. Collins;K. Martin;L. Bennett;A. Haugen;P. Bushel;E. Mu
通讯作者：
C. Steenbergen;C. Afshari;J. Petranka;J. Collins;K. Martin;L. Bennett;A. Haugen;P. Bushel;E. Mu
影响因子：
5
作者：
Penumathsa, Suresh Varma;Thirunavukkarasu, Mahesh;Maulik, Nilanjana
通讯作者：
Maulik, Nilanjana