P2X(7) inhibition in stellate ganglia prevents the increased sympathoexcitatory reflex via sensory-sympathetic coupling induced by myocardial ischemic injury

Brain Res Bull. 2013 Jul:96:71-85. doi: 10.1016/j.brainresbull.2013.05.004. Epub 2013 May 17.

Abstract

Purinergic signaling has been found to participate in the regulation of cardiovascular function. In this study, using a rat myocardial ischemic injury model, the sympathoexcitatory reflex mediated by P2X7 receptor via sensory-sympathetic coupling between cervical dorsal root ganglia (DRG) nerves and stellate ganglia (SG) nerves was explored. Our results showed that the systolic blood pressure, heart rate, serum cardiac enzymes concentrations, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations were increased, and the expression levels of P2X7 mRNA and protein in DRG and SG were up-regulated after myocardial ischemic injury. Administration of brilliant blue G (BBG), a selective P2X7 antagonist, decreased the elevation of systolic blood pressure, heart rate, serum cardiac enzyme, IL-6 and TNF-α, and inhibited the up-regulated expression of P2X7 mRNA and protein in DRG and SG after myocardial ischemic injury. Retrograde tracing test showed that there were calcitonin gene-related peptide sensory nerves and substance P sensory nerves sprouting from DRG to SG, which played an important role in the development of myocardial ischemic injury. The up-regulated P2X7 receptor expression levels on the surface membrane of satellite glial cells contributed to the activation of sensory-sympathetic coupling, which in turn facilitated the sympathoexcitatory reflex. BBG can inhibit the activation of satellite glial cells and interrupt the generation of sensory-sympathetic coupling in the cervical sympathetic ganglia after the myocardial ischemic injury. Taken together, these findings may provide a new therapeutic approach for treating coronary heart disease, hypertension and other cardiovascular diseases.

Keywords: Dorsal root ganglia; Myocardial ischemic injury; P2X(7) receptor; Sensory-sympathetic coupling; Stellate ganglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology
  • Purinergic P2X Receptor Antagonists / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X7 / metabolism*
  • Reflex / physiology*
  • Rosaniline Dyes / pharmacology
  • Signal Transduction / physiology
  • Stellate Ganglion / drug effects
  • Stellate Ganglion / metabolism*
  • Substance P / metabolism

Substances

  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Rosaniline Dyes
  • Substance P
  • Calcitonin Gene-Related Peptide
  • coomassie Brilliant Blue