Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction
Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction
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DOI：
10.1152/ajpheart.00643.2007
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发表时间：
2008-01-01
影响因子：
4.8
通讯作者：
Kangawa, Kenji
中科院分区：
文献类型：
--
作者：
Soeki, Takeshi;Kishimoto, Ichiro;Kangawa, Kenji
最近的一项研究表明，外源性胃饥饿素可能会降低有意识的兔子的肾交感神经活动。在本研究中，我们研究了ghrelin政府将是否通过抑制心脏交感神经活动来减弱心肌梗死（MI）后左室（LV）重构。Sprague-Dawley大鼠心肌梗死术后第2天起连续2周给予胃饥饿素（100 μ g/kg sc，每日2次，n = 15）或生理盐水（n = 15）。通过超声心动图、血流动力学、组织病理学和基因分析评估胃饥饿素对心脏重塑的影响。此外，采用遥测系统功率谱分析方法，对有意识心肌梗死大鼠给予胃饥饿素（100 μ g/ kg sc, n = 6）前后的自主神经功能进行研究。与盐水处理大鼠相比，胃饥饿素处理大鼠心肌梗死引起的左室增大明显减弱。此外，与盐水处理的心肌梗死大鼠相比，胃饥饿素处理的心肌梗死大鼠左室舒张末压明显降低，左室压峰值上升和下降速率增加。此外，胃饥饿素减弱了非梗死区形态胶原体积分数的增加，这伴随着胶原I和III mRNA水平的抑制。重要的是，2周的胃饥饿素治疗显著地抑制了mi诱导的心率和血浆去甲肾上腺素浓度的增加，使其达到与假手术对照组相似的水平。急性给药胃饥饿素可降低心肌梗死大鼠心率变异性的低频与高频频谱之比（P < 0.01）。总之，这些数据提示胃饥饿素在心肌梗死后早期作为一种新的心脏保护激素的潜在作用。
A recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether ghrelin administration would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via the suppression of cardiac sympathetic activity. Ghrelin (100 mu g/kg sc, twice daily, n = 15) or saline (n = 15) were administered for 2 wk from the day after MI operation in Sprague-Dawley rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, histopathological, and gene analysis. In addition, before and after ghrelin (100 mu g/ kg sc, n = 6) was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. In ghrelin-treated rats, LV enlargement induced by MI was significantly attenuated compared with saline-treated rats. In addition, there was a substantial decrease in LV end-diastolic pressure and increases in the peak rate of the rise and fall of LV pressure in ghrelin-treated MI rats compared with saline-treated MI rats. Furthermore, ghrelin attenuated an increase in morphometrical collagen volume fraction in the noninfarct region, which was accompanied by the suppression of collagen I and III mRNA levels. Importantly, a 2-wk administration of ghrelin dramatically suppressed the MI-induced increase in heart rate and plasma norepinephrine concentration to the similar levels as in sham-operated controls. Moreover, acute administration of ghrelin to MI rats decreased the ratio of the low-to-high frequency spectra of heart rate variability (P < 0.01). In conclusion, these data suggest the potential usefulness of ghrelin as a new cardioprotective hormone early after MI.