Submitted on October 17, 2007
Accepted on March 26, 2008
Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in heart failure
Allison C Kleiber1, Hong Zheng2, Harold D. Schultz1, Jacob D. Peuler3, and Kaushik P Patel1*
1 Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
2 Department of Cellular and Integrative Physiology, University of Nebraska Medical Cener, Omaha, Nebraska, United States
3 Department of Pharmacology, Midwestern University, Downers Grove, Illinois, United States
* To whom correspondence should be addressed. E-mail: kpatel{at}unmc.edu.
Exercise training (ExT) normalizes the increased sympathetic outflow in heart failure (HF), but the mechanisms are not known. We hypothesized ExT would normalize the augmented glutamatergic mechanisms mediated by NMDA receptors within the PVN that occurs with HF. Four groups of rats were used: 1) 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 three weeks of treadmill running. In 
-chloralose-urethane-anesthetized rats, the increase in renal sympathetic nerve activity (RSNA) 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 or Sham ExT groups. Relative NMDA receptor subunit NR1 mRNA expression was 63% higher in the HF Sed group compared to the Sham Sed group, but in the HF ExT group was not different from the Sham Sed or Sham ExT groups. NR1 receptor subunit protein expression was increased 87% in the HF Sed group compared to the Sham Sed group but in the HF ExT group was not significantly different from the Sham Sed or 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.
