Effects of chronic lead exposure on the sympathoexcitatory response associated with the P2X7 receptor in rat superior cervical ganglia.

Abstract

Chronic lead exposure frequently brings about increased blood pressure and other cardiovascular diseases associated with autonomic nervous dysfunction. Purinergic signaling is involved in the development of abnormal sympathoexcitatory response due to myocardial ischemic injury. However, the potential implication of P2X7 receptor in altered sympathoexcitatory response caused by chronic lead exposure and the underlying mechanisms remain unclear. In this study, a rat model of chronic lead exposure was used to explore the changes in sympathoexcitatory response and possible involvement of P2X7 receptor in the superior cervical ganglion (SCG). Rats were divided into three groups called control, low lead and high lead groups according to daily lead exposure levels, i.e. 0, 0.5 and 2 g/L respectively. One year later, changes in P2X7 receptor expression in SCG, sympathetic nerve activity and myocardial function were measured for these rats. Our results showed that increased blood pressure and heart rate, decreased heart rate variability, enhanced cervical sympathetic nerve discharge, higher phosphorylation of ERK1/2, and up-regulated protein and mRNA levels of P2X7 expression in SCG occurred after lead exposure. In addition, double-label immunofluorescence staining of P2X7 receptor and glutamine synthetase (GS) revealed activation of the satellite glial cells of SCG by lead exposure. Moreover, knockdown of P2X7 could effectively relief the effect of lead exposure on enhanced expression of P2X7 receptor and GS. Thus our data suggest that the up-regulation of P2X7 receptor activity in satellite glial cells of SCG may contribute to the raised sympathoexcitatory response due to chronic lead exposure.