Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus.
Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus.
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血管紧张素受体改变心肌梗塞诱导的豚鼠心丛重塑。
DOI：
10.1152/ajpregu.00004.2015
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ardell,JeffreyL
中科院分区：
文献类型：
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作者：
Hardwick,JeanC;Ryan,ShannonE;Powers,EmilyN;Southerland,EMarie;Ardell,JeffreyL
神经体液重塑是心脏病发生发展的基础。本研究观察了血管紧张素转换酶抑制剂(卡托普利，3 mg·kg-1−1·day−1)、AT1受体拮抗剂(氯沙坦3 mg·kg-1−1·day−1)和AT2受体激动剂(CGP42 112A，0 14 mg·kg−1·day−1)对慢性心肌梗死(MI)后豚鼠心内神经丛重构的影响。手术诱导心肌梗死，动物恢复6~7wk，有或无药物治疗。用心神经丛整束的细胞内电压记录来监测神经元对去甲肾上腺素(NE)、毒扁豆碱激动剂(苯妥英酚)或Ang II的反应的变化。MI使神经元对NE的兴奋性增加，对Ang II的敏感性降低。卡托普利治疗的MI动物在应用NE时神经元的兴奋性增加，而CGP42112A治疗的MI动物没有。与未治疗的心肌梗塞相比，接受氯沙坦治疗的MI动物对去甲肾上腺素的兴奋性没有改变，但这些动物确实表现出增强的突触效力。这种对突触功能的影响可能是由于突触前AT1受体，因为Ang II能够减少对照组动物对神经纤维刺激的输出，而这种影响可以通过在浴液中加入氯沙坦来阻止。Western印迹分析AT受体表达显示，心肌梗死后AT1和AT2受体均减少，这一现象可被三种药物逆转。这些数据表明，心肌梗死后豚鼠心神经丛的神经元重构部分是通过AT1和AT2受体的激活而介导的。
Neurohumoral remodeling is fundamental to the evolution of heart disease. This study examined the effects of chronic treatment with an ACE inhibitor (captopril, 3 mg·kg−1·day−1), AT1receptor antagonist (losartan, 3 mg·kg−1·day−1), or AT2receptor agonist (CGP42112A, 0.14 mg·kg−1·day−1) on remodeling of the guinea pig intrinsic cardiac plexus following chronic myocardial infarction (MI). MI was surgically induced and animals recovered for 6 or 7 wk, with or without drug treatment. Intracellular voltage recordings from whole mounts of the cardiac plexus were used to monitor changes in neuronal responses to norepinephrine (NE), muscarinic agonists (bethanechol), or ANG II. MI produced an increase in neuronal excitability with NE and a loss of sensitivity to ANG II. MI animals treated with captopril exhibited increased neuronal excitability with NE application, while MI animals treated with CGP42112A did not. Losartan treatment of MI animals did not alter excitability with NE compared with untreated MIs, but these animals did show an enhanced synaptic efficacy. This effect on synaptic function was likely due to presynaptic AT1receptors, since ANG II was able to reduce output to nerve fiber stimulation in control animals, and this effect was prevented by inclusion of losartan in the bath solution. Analysis of AT receptor expression by Western blot showed a decrease in both AT1and AT2receptors with MI that was reversed by all three drug treatments. These data indicate that neuronal remodeling of the guinea pig cardiac plexus following MI is mediated, in part, by activation of both AT1and AT2receptors.