Sedentary conditions and enhanced responses to GABA in the RVLM: role of the contralateral RVLM

By: Maryetta D. Dombrowski and Patrick J. Mueller

Am J Physiol Regul Integr Comp Physiol 2017

Overactivity of the sympathetic nervous system has been found to be associated with a sedentary lifestyle, which in turn increases the risk factor for cardiovascular disease. The RVLM regulates the discharge of sympathetic nerves, and the RVLM itself is regulated by excitatory (glutamate) and inhibitory (GABA) neurotransmitters. In previous studies it has been reported that sedentary conditions increase GABAergic modulation of sympathoexcitation in the RVLM. The first purpose of this study was to determine if sedentary conditions enhance GABA sensitivity in the RVLM compared to physically active conditions. Other previous studies found that contralateral inputs involved in the baroreflex pathway may buffer responses when GABA is unilaterally injected into the RVLM. Therefore, the second purpose of this study was to examine those potential buffering differences between the right and left RVLM in both sedentary and physically active rats.

Male Sprague-Dawley rats were used and divided into physically active groups (provided with running wheels) and sedentary groups (no running wheels) who were housed under those conditions for 12-15 weeks. Afterwards, acute RVLM microinjections were performed with triple barrel pipettes containing the following GABA concentrations: 0.3, 3, 30, 300, and 600 mM. These microinjections were performed in the left RVLM and the MAP, HR, and SSNA activity were recorded. To test whether the buffering occurred, long acting GABA (muscimol) was injected into the right RVLM. Then, the GABA microinjections were repeated in the left side 15 minutes later followed by a muscimol injection into the left RVLM to inhibit neuronal activity and confirm that the right RVLM was previously inhibited. Lastly, bilateral sinoaortic denervations were performed in both physically active and sedentary groups.

The findings of this study were three-fold. First, they found that when the RVLM was directly inhibited with increasing doses of GABA, dose-dependent decreases in MAP and SSNA occurred in both the sedentary and physically active groups. However, there was no difference in response between the groups. Second, when the right RVLM was inhibited with muscimol and then microinjections of GABA proceeded in the left RVLM, there was enhanced sympathoexcitatory responses in the sedentary rats but not the physically active rats. Third, in both groups denervation of the arterial baroreceptor afferents showed no difference in sympathoinhibitory responses with the increasing GABA concentrations microinjected into the left RVLM.

The conclusion of this study was that in sedentary rats the contralateral RVLM compensates for decreases in sympathetic outflow when acute inhibition occurs in the opposing RVLM. This, however, does not occur in physically active rats. In addition, the neurons that are not inhibited in the RVLM (for example the ones in the left RVLM when the right is inhibited) become more sensitive to GABAergic inhibition in sedentary rats but not in physically active rats.

-L. Matus