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

Abstract

P2X receptors participate in cardiovascular regulation and disease. After myocardial ischemic injury, sensorysympathetic coupling between rat cervical DRG nerves and superior cervical ganglia (SCG) facilitated sympathoexcitatory action via P2X 7 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 P2X 7 mRNA and protein in SCG were also upregulated. However, these alterations diminished after treatment of myocardial ischemic (MI) rats with the P2X 7 antagonist oxATP. After siRNA P2X 7 in MI rats, the systolic blood pressure, heart rate, serum cardiac enzymes, the expression levels of the satellite glial cell (SGC) or P2X 7 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 P2X 7 receptor promoted the activation of SGCs in SCG, resulting in the formation of sensory-sympathetic coupling which facilitated the sympathoexcitatory action. P2X 7 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.

Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

“…Previous studies in our laboratory showed that the upregulation of the P2X 3 , P2X 2/3 , and P2X 7 receptors in the stellate ganglia (SG) and superior cervical ganglia (SCG) after MI injury resulted in increased blood pressure and HR by strengthening the activity of the sympathetic postganglionic neurons [15,[18][19][20][21][22][23][24][25][26][27][28]. Our works also showed that P2X 3 , P2X 2/3 , or P2X 7 antagonists decreased the elevated SBP and HR and alleviated the arrhythmia induced by myocardial ischemia [15,[18][19][20][21][22][23][24][25][26][27][28][29]. NONRATT021972 is a lncRNA [30] [http://www.noncode.…”

“…b The histogram shows the normalized, mean peak current (mean ± S, n = 12, **P < 0.01, compared to the con group; ## P < 0.01 vs the MI group). NONRATT021972 siRNA decreased the BzATP-induced currents in HEK293 cells expressing the hP2X 7 receptor by an increase in blood pressure and sympathetic nerve activity [14,19,24,29]. Previous data from our laboratory showed that the serum ATP concentration was increased after the MI injury [32].…”

Cardiac purinergic signalling in health and disease

“…There is up-regulation of P2X7R in rat superior cervical ganglia (SCG) after myocardial ischaemic injury [589]. Sensory-sympathetic coupling in SCG after myocardial ischaemic injury facilitates sympathoexcitatory action via upregulated P2X7R [590]. The P2X7R antagonist brilliant blue G acting on stellate ganglia prevented the increased sympathoexcitatory reflex via sensory-sympathetic coupling induced by myocardial ischaemic injury [591].…”

LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells

“…Evidence has indicated that the P2X7 receptor was involved in the process of inflammatory response and release of inflammatory mediators [20,21]. Our previous studies also showed that the P2X7 receptor played a major role in the transmission of inflammatory signals and contributed to the pathological process of sympathetic injury [6,10,[22][23][24][25].…”

“…This finding suggests nc021972 may be involved in the pathophysiologic processes related to the sympathetic neuron under the setting of diabetes. Our previous studies have shown that the P2X7 receptor was implicated in the pathological injury of sympathetic nerves [6,10,[22][23][24][25]. The aim of the study was to examine the effects of nc021972 small interference RNA (siRNA) on the P2X7 receptor and its possible role in neuroinflammation induced by elevated glucose and FFAs in PC12 cells.…”