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Sensory–sympathetic coupling in superior cervical ganglia after myocardial ischemic injury facilitates sympathoexcitatory action via P2X7 receptor

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Abstract

P2X receptors participate in cardiovascular regulation and disease. After myocardial ischemic injury, sensory–sympathetic coupling between rat cervical DRG nerves and superior cervical ganglia (SCG) facilitated sympathoexcitatory action via P2X7 receptor. The results showed that after myocardial ischemic injury, the systolic blood pressure, heart rate, serum cardiac enzymes, IL-6, and TNF-α were increased, while the levels of P2X7 mRNA and protein in SCG were also upregulated. However, these alterations diminished after treatment of myocardial ischemic (MI) rats with the P2X7 antagonist oxATP. After siRNA P2X7 in MI rats, the systolic blood pressure, heart rate, serum cardiac enzymes, the expression levels of the satellite glial cell (SGC) or P2X7 were significantly lower than those in MI group. The phosphorylation of ERK 1/2 in SCG participated in the molecular mechanism of the sympathoexcitatory action induced by the myocardial ischemic injury. Retrograde tracing test revealed the sprouting of CGRP or SP sensory nerves (the markers of sensory afferent fibers) from DRG to SCG neurons. The upregulated P2X7 receptor promoted the activation of SGCs in SCG, resulting in the formation of sensory–sympathetic coupling which facilitated the sympathoexcitatory action. P2X7 antagonist oxATP could inhibit the activation of SGCs and interrupt the formation of sensory–sympathetic coupling in SCG after the myocardial ischemic injury. Our findings may benefit the treatment of coronary heart disease and other cardiovascular diseases.

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Abbreviations

ATP:

Adenosine triphosphate

CGRP:

Calcitonin gene-related peptide

CK:

Creatine kinase

CK-MB:

Creatine kinase isoform MB

cTn-I:

Cardiac troponin I

DRG:

Dorsal root ganglia

ECG:

Electrocardiogram

ELISA:

Enzyme-linked immunosorbent assay

ERK1/2:

Extracellular signal-regulated protein kinases

GS:

Glutamine synthetase

HRP:

Horseradish peroxidase

IOD:

Integrated optical density

IL-6:

Interleukin-6

ISH:

In situ hybridization

LCA:

Left coronary artery

LDH:

Lactate dehydrogenase

MI:

Myocardial ischemic

NeuN:

Neuronal Nuclei

oxATP:

Oxidized ATP (ATP with the 2′- and 3′-hydroxyl moieties oxidized to aldehydes by periodate treatment)

PCR:

Polymerase chain reaction

p-ERK1/2:

Phosphorylated extracellular signal-regulated protein kinases

SP:

Substance P

TH:

Tyrosine hydroxylase

TNF-α:

Tumor necrosis factor-α

SGCs:

Satellite glial cells

SCG:

Superior cervical ganglia

siRNA:

Small interference RNA

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Acknowledgments

This work was supported by grants (№s. 81171184, 31060139, 30860086, 30660048, and 81200853) from National Natural Science Foundation of China, grants (№s. 0640042 and 2008GZY0029) from Natural Science Foundation of Jiangxi Province, grants (№s. 2010BSA09500 and 20111BBG70009-1) from Technology Pedestal and Society Development Project of Jiangxi Province, and grant (№. GJJ13155) from Education Department of Jiangxi Province.

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  1. Department of Physiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Jun Liu, Guilin Li, Haiying Peng, Guihua Tu, Fanjun Kong, Shuangmei Liu, Yun Gao, Hong Xu, Shuyi Qiu, Bo Fan, Qicheng Zhu, Shicheng Yu, Chaoran Zheng, Bing Wu, Lichao Peng, Miaomiao Song, Qin Wu, Guodong Li & Shangdong Liang

  2. Key Laboratory of Basic Medicine, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Shangdong Liang

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  1. Jun Liu
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Liu, J., Li, G., Peng, H. et al. Sensory–sympathetic coupling in superior cervical ganglia after myocardial ischemic injury facilitates sympathoexcitatory action via P2X7 receptor. Purinergic Signalling 9, 463–479 (2013). https://doi.org/10.1007/s11302-013-9367-2

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