Downregulation of P2Y₁₂ in the superior cervical ganglia alleviates abnormal sympathetic activity after myocardial ischemia

Abstract

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y receptor is expressed in satellite glial cells (SGCs). This study seeks to clarify whether the P2Y receptor is involved in the sympathoexcitation reflex after myocardial ischemia (MI). MI model was induced by occlusion of the left coronary artery. P2Y were assayed by real time PCR and Western blotting. Our results showed that expression levels of P2Y mRNA and protein were significantly higher in the MI group than in the sham group. Administration of P2Y short hairpin RNA (shRNA) caused downregulation of the P2Y receptor in the SCG. In MI rats plus P2Y shRNA treatment group, the abnormal changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), electrocardiograms (ECGs), and cardiac tissue structures were alleviated. When the treatment of P2Y shRNA in MI rats, upregulated co-expression values of P2Y and glial fibrillary acidic protein (GFAP), the upregulation of tumor necrosis factor α (TNF-α) and phosphorylated P38 mitogen activated protein kinase (p-P38 MAPK) in the SCG were decreased. Downregulation of the P2Y receptor in the SCG after MI may improve cardiac function by alleviating the sympathoexcitatory reflex.

Involvement of P2Y12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy

“…It is also expressed in SGCs of SG [27]. Upregulation P2Y 12 receptor in the SGCs of superior cervical ganglia participates in the sympatho-excitatory reflex after myocardial ischemia [23]. Second, overexpression of P2Y 12 receptor in SG increased blood pressure, heart rate and cervical SND in non-diabetic rats whereas treatment of P2Y 12 shRNA could decrease the elevated blood pressure, heart rate and cervical SND occurring in diabetic rats.…”

“…The autonomic ganglia include sympathetic and parasympathetic ones. The cervical sympathetic nervous system contributes to the maintenance of cardiovascular homeostasis [23]. Cardiac sympathetic innervation is largely made by the superior cervical ganglia (SCG) and the stellate ganglia (SG) [24].…”

“…Axotomy, inflammation, and other injuries can activate the SGCs of primary sensory ganglia [28]. P2Y 12 receptor is expressed in SGCs [23,[29][30][31] and may participate in bidirectional neuronal-glial communications [15,32]. However, little is known whether P2Y 12 receptor is implicated in DCAN.…”

Baicalin Depresses the Sympathoexcitatory Reflex Induced by Myocardial Ischemia via the Dorsal Root Ganglia

“…Purinergic signaling has pivotal roles in physiological and pathophysiological cardiovascular processes ( Vassort, 2001 ; Erlinge and Burnstock, 2008 ; Kennedy et al, 2013 ; Burnstock and Pelleg, 2015 ). Purinergic P2Y receptors have been implicated in the treatment of cardiovascular diseases ( Nishimura et al, 2017 ; Zou et al, 2017 ). In the present study, we demonstrated that both the expression levels of P2Y 12 receptor mRNA and protein in DRG of MI rats were increased.…”

“…P2Y 12 receptors are expressed in SGCs of DRG ( Kobayashi et al, 2008 ; Katagiri et al, 2012 ). Additionally, P2Y 12 receptors expressed in SCG are involved in mediating the sympathoexcitatory reflex ( Zou et al, 2017 ). DRGs have primary sensory neurons, however, the role of the P2Y 12 receptor in DRG SGCs during MI remains to be investigated.…”