Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels.
Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels.
复制标题
促红细胞生成素对幼兔的急性心脏保护作用是通过激活蛋白激酶和钾通道介导的。
DOI：
10.1007/s00395-004-0455-x
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发表时间：
2004
影响因子：
9.5
通讯作者：
Baker,JohnE
中科院分区：
文献类型：
--
作者：
Shi,Yang;Rafiee,Parvaneh;Su,Jidong;PritchardJr,KirkwoodA;Tweddell,JamesS;Baker,JohnE
摘要：促红细胞生成素对心肌缺血有保护作用，但其机制尚不清楚。我们确定了促红细胞生成素（0.5 - 10.0 U/ml）是否赋予幼兔心脏急性心脏保护作用，以及蛋白激酶、一氧化氮合酶和钾通道对潜在机制的贡献。从含氧量正常的新西兰白色幼兔（n=8/组）分离心脏并以Langendorff模式灌注。在30 min全脑无血流缺血和35 min再灌注前，在稳态条件下记录双心室功能。促红细胞生成素的管理15分钟缺血前立即导致浓度依赖性增加恢复左，右心室发展的压力在兔心脏心肌缺血和再灌注后。促红细胞生成素的最佳浓度为1.0 U/ml，可使产生的压力最大限度地恢复。促红细胞生成素（1.0U/ml）处理导致PKC、p38 MAP激酶和p42/44 MAP激酶磷酸化。蛋白激酶抑制剂SB 203580（p38 MAP激酶）、PD 98059（p42/44 MAP激酶）和白屈菜红碱（PKC）以及钾通道阻断剂格列本脲、HMR 1098、5-HD和Paxilline可阻断促红细胞生成素的心肌保护作用。促红细胞生成素（1.0U/ml）作用15 min前（2.3 ± 0.9nmol/min/g）和作用15 min后（2.4 ± 1.9nmol/min/g），心肌释放的亚硝酸盐和硝酸盐无明显差异。L-NAME和L-NMA不能阻断促红细胞生成素的心肌保护作用。我们的结论是红细胞生成素快速激活钾通道和蛋白激酶是一个重要的新机制，增加心脏保护。
Abstract.Erythropoietin is protective against cardiac ischemia, but the underlying mechanisms are unknown. We determined whether erythropoietin (0.5 – 10.0 U/ml) confers acute cardioprotection in infant rabbit hearts and the contribution of protein kinases, nitric oxide synthase and potassium channels to the underlying mechanism. Hearts from normoxic infant New Zealand White rabbits (n=8/group) were isolated and perfused in the Langendorff mode. Biventricular function was recorded under steady-state conditions prior to 30 min global no-flow ischemia and 35 min reperfusion. Administration of erythropoietin for 15 min immediately prior to ischemia resulted in a concentration-dependent increase in recovery of left and right ventricular developed pressure in rabbit hearts following myocardial ischemia and reperfusion. The optimal concentration of erythropoietin that afforded maximum recovery of developed pressure was manifest at 1.0 U/ml. Erythropoietin (1.0 U/ml) treatment resulted in phosphorylation of PKC, p38 MAP kinase and p42/44 MAP kinase. The cardioprotective effects of erythropoietin were abolished by the protein kinase inhibitors SB203580 (p38 MAP kinase), PD98059 (p42/44 MAP kinase) and chelerythrine (PKC) as well as the potassium channel blockers glibenclamide, HMR 1098, 5-HD and Paxilline. Nitrite and nitrate release from hearts before (2.3 ± 0.9 nmol/min/g) and after (2.4 ± 1.9 nmol/min/g) 15 min treatment with erythropoietin (1.0 U/ml) were not different. L-NAME and L-NMA did not block the cardioprotective effect of erythropoietin. We conclude the rapid activation of potassium channels and protein kinases by erythropoietin represents an important new mechanism for increasing cardioprotection.