Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease
Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease
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DOI：
10.1152/ajpregu.00223.2012
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发表时间：
2012-11-01
影响因子：
2.8
通讯作者：
Ardell, Jeffrey L.
中科院分区：
文献类型：
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作者：
Hardwick, Jean C.;Southerland, E. Marie;Ardell, Jeffrey L.
Hardwick JC，Southerland EM，Girasole AE，Ryan SE，Negrotto S，Ardell JL.心脏内在神经元的重塑：β-肾上腺素能受体阻滞剂对慢性心脏病豚鼠模型的影响。Am J Physiol Regul Integr Comp Physiol 303：R950-R958，2012年。首次发表于2012年8月29日; doi：10.1152/ajpregu.00223.2012.-慢性心脏病诱导心脏组织和相关神经元成分的重塑。慢性心脏病的治疗通常涉及肾上腺素能受体的药物阻断。本研究检测了慢性心脏病动物在存在或不存在肾上腺素能阻断的情况下，豚鼠心脏固有神经元对自主调节剂的神经元敏感性的特异性变化。心肌梗死（MI）是通过结扎冠状动脉和相关静脉的背面的心脏。压力超负荷（PO）是由降背主动脉（类似于20%的收缩）的束带诱导的。使动物恢复2周，然后植入含有噻吗洛尔（2 mg.kg（-1）.day（-1））或溶媒的渗透泵（Alzet），总共进行6-7周的药物治疗。在终止时，使用来自整个心脏丛中的单个神经元的细胞内记录来评估生理反应的变化。噻吗洛尔给药未抑制MI和PO动物中观察到的对去甲肾上腺素敏感性增加，但确实抑制了血管紧张素II对去甲肾上腺素诱导的神经元兴奋性增加的刺激作用。噻吗洛尔治疗还抑制了在PO动物中观察到的刺激纤维束的突触诱发动作电位的增加。这些结果表明，β-肾上腺素能阻滞剂可以抑制内在心脏神经丛内重塑的特定方面。此外，在活动性心脏病状态下优先观察到这种效应，表明β受体在动态疾病进展期间对重塑的影响更大。
Hardwick JC, Southerland EM, Girasole AE, Ryan SE, Negrotto S, Ardell JL. Remodeling of intrinsic cardiac neurons: effects of beta-adrenergic receptor blockade in guinea pig models of chronic heart disease. Am J Physiol Regul Integr Comp Physiol 303: R950-R958, 2012. First published August 29, 2012; doi:10.1152/ajpregu.00223.2012.-Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (similar to 20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg.kg(-1).day(-1)) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that beta-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the beta-receptors were more influential on remodeling during dynamic disease progression.