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

Kleiber AC, Zheng H, Schultz HD, Peuler JD, Patel KP.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.

Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1863-72. Epub 2008 Apr 2.

 

Heart failure patients have high sympathetic outflow. Studies have shown that exercise training (ExT) normalizes muscle sympathetic nerve activity (MSNA), however the mechanisms are unknown. In this study the authors hypothesized the mechanisms by which ExT reduces MSNA is by normalizing the increased glutamatergic mechanisms within the PVN. Previous studies from the lab have shown that when PVN was injected with N-methyl-D-aspartic acid (NMDA) (a glutamate agonist that acts at the NMDA receptor), there was augmented renal sympathetic nerve activity (RSNA) in the heart failure rats compared to their normalized control. In this study the authors determined whether ExT reduces the RSNA response to NMDA in heart failure. Further they also determined whether ExT normalizes the expression of NMDA receptor subunit NR1 in heart failure rats. Heart failure was induced by left coronary artery ligation. Three weeks after inducing heart failure animals were given ExT using treadmills for 3 weeks. The animals ran for a period of 1hr/day at a speed of 20-25 m/min. RSNA and microinjection procedures were performed 6-8 wk after heart failure surgery or sham surgery. Microinjection of NMDA to hearf failure rats that are on ExT produced no changes in RSNA or MAP compared to control. This shows that ExT normalizes the augmented RSNA in response to NMDA microinjection in the PVN of heart failure rats. ExT also reduced the gene expression and protein levels of NMDA receptor subunit NR1 in the heart failure rats compared to heart failure rats that were not on ExT suggesting a possible mechanism by which RSNA responses to NMDA injected in to the PVN. These results suggest normalization of glutamatergic mechanisms is one possible way by which ExT normalizes sympathetic outflow in heart failure.

 

- Madhan