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Effect of nerve growth factor on sympathetic neuronal function in heart failure after myocardial infarction

神经生长因子对心肌梗死后心力衰竭交感神经功能的影响

基本信息

批准号：
12670654
负责人：
INOUE Hiroshi
金额：
$ 2.18万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670654/
关键词：
myocardial ischemia heart failure nearve growth factor sympathetic nerve catecholamine beta-receptor

项目摘要

An activation of sympathetic nervous system is one of major pathophysiological abnormalities which progress heart failure. The magnitude of sympathetic activation relates to prognosis in patients with heart failure. Therefore, direct inhibition of sympathetic activity might be an effective approach to therapy of heart failure. In the present study, we investigated. 1) effects of peripheral sympathoinhibition by guanethidine on mortality and cardiac function in rats after myocardial infarction, and 2) effects of nerve growth factor (NGF) and anti-NGF on sympathetic neuronal function in myocardial ischemia-reperfusion injury. NGF is a neurotrophic factor that is necessary for survival and regeneration of peripheral sympathetic nerves. It was shown that NGF is released acutely from the ischemic myocardium.In chronic treatment with high dose guanethidine (10 mg/kg/day) from 2 days before the induction of myocardial infarction, hemodynamic function was not affected in sham-operated rats des … More pite the depletion of myocardial norepinephrine (NE). The 28-day mortality of infracted rats treated with the high dose guanethidine increased markedly (96%), as compared with infarcted rats without guanethidine (52%). In contrast, low dose guanethidine (1 mg/kg/day) improved the mortality (6%) and inhibited the ventricular remodeling. Cardiac sympathetic neuronal function was assessed by ^<131>I-metaiodobenzylguanedine (MIBG), an analogue of NE, in a rat of 15-min coronary artery occlusion and reperfusion. NGF decreased cardiac MIBG uptake in both ischemic and non-ischemic regions of left ventricle. Anti-NGF however increased it in both regions. MIBG uptake was reduced in ischemic region, but neither NGF nor anti-NGF altered the ischemic/non-ischemic uptake ratio.In summary, "moderate" sympathoinhibition might be favorable for prognosis or inhibition of ventricular remodeling in heart failure after myocardial infarction, but a powerful sympathoinhibition that depletes myocardial NE might be harmful. A modulation of excess sympathetic nerve activation by anti-NGF may be effective for the treatment of heart failure. Less

交感神经系统的激活是导致心力衰竭的主要病理生理异常之一。交感神经激活的程度与心力衰竭患者的预后有关。因此，直接抑制交感神经活动可能是治疗心力衰竭的有效方法。在本研究中，我们进行了调查。1)外周交感神经抑制剂乙啶对心肌梗死后大鼠死亡率和心功能的影响; 2）神经生长因子（NGF）及其拮抗剂对心肌缺血再灌注损伤交感神经功能的影响。神经生长因子是周围交感神经存活和再生所必需的神经营养因子。结果表明，缺血心肌可迅速释放NGF，在诱导心肌梗塞前2天开始给予大剂量乙啶（10 mg/kg/d）慢性治疗，对假手术大鼠的血流动力学功能无影响。 ...更多信息心肌去甲肾上腺素（NE）耗竭。与未使用乙啶的梗塞大鼠（52%）相比，使用高剂量乙啶的梗塞大鼠的28天死亡率显著增加（96%）。低剂量乙啶（1 mg/kg/d）可降低死亡率（6%），抑制心室重构。用去甲肾上腺素（NE）<131>类似物~（45）I-间碘苄基胍（MIBG）测定大鼠冠状动脉阻断15分钟再灌注后心脏交感神经元的功能。NGF减少左心室缺血和非缺血区域的心脏MIBG摄取。然而，抗神经生长因子增加了它在这两个地区。结论：“中度”交感神经抑制可能有利于心肌梗死后心力衰竭患者的预后或抑制心室重构，但过度抑制交感神经抑制可能不利于心肌NE的耗竭。通过抗NGF调节过度的交感神经激活可能对心力衰竭的治疗有效。少