Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in heart failure

Allison C. Kleiber, Hong Zheng, Harold D. Schultz, Jacob D. Peuler, Kaushik P. Patel

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Exercise training (ExT) normalizes the increased sympathetic outflow in heart failure (HF), but the mechanisms are not known. We hypothesized that ExT would normalize the augmented glutamatergic mechanisms mediated by N-methyl-D-aspartic acid (NMDA) receptors within the paraventricular nucleus (PVN) that occur with HF. Four groups of rats were used: 1) sham-operated (Sham) sedentary (Sed), 2) Sham ExT, 3) HF Sed, and 4) HF ExT. HF was induced by left coronary artery ligation, and ExT consisted of 3 wk of treadmill running. In α-chloralose-urethane-anesthetized rats, the increase in renal sympathetic nerve activity in response to the highest dose of NMDA (200 pmol) injected into the PVN in the HF Sed group was approximately twice that of the Sham Sed group. In the HF ExT group the response was not different from the Sham Sed and Sham ExT groups. Relative NMDA NR1 receptor subunit mRNA expression was 63% higher in the HF Sed group compared with the Sham Sed group but in the HF ExT group was not different from the Sham Sed and Sham ExT groups. NR1 receptor subunit protein expression was increased 87% in the HF Sed group compared with the Sham Sed group but in the HF ExT group was not significantly different from the Sham Sed and Sham ExT groups. Thus one mechanism by which ExT alleviates elevated sympathetic outflow in HF may be through normalization of glutamatergic mechanisms within the PVN.

Original languageEnglish (US)
Pages (from-to)R1863-R1872
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • N-methyl-D-aspartic acid receptors
  • Paraventricular nucleus
  • Sympathetic nerve activity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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