Research has shown that the development of cardiovascular diseases, such as hypertension, are linked to a sedentary lifestyle. Overactivity of the sympathetic nervous system has been shown to contribute to hypertension through its regulation of resting blood pressure through tonic activation of the RVLM. The RVLM is regulated through inhibitory signals by the CVLM and its GABAergic projections. The GABA projections are altered under different disease states, thus changing the ability of the RVLM to maintain a “normal” sympathetic outflow to control resting blood pressure. However, previous studies have shown that brain regions that exist on both sides of the brain, like the RVLM, contribute to a compensatory buffering input in the contralateral side. Thus, the study hypothesized that the contralateral RVLM would help to compensate for decreased sympathoinhibition at this level, thus helping to maintain blood pressure. The primary focus of the research was to determine whether sedentary conditions enhanced the sensitivity of GABA when compared to active conditions, while simultaneously establishing if there is a buffering response from the contralateral RVLM.
The experiment was completed through unilateral microinjections of GABA within the left RVLM at 0.3, 3, 30, 300, or 600mM concentrations. Splanchnic sympathetic nerve activity (sSNA) was measured at baseline and after the GABA injection, as well as mean arterial blood pressure (MAP) and heart rate (HR). Initially, Both sides of the RVLM remained intact while performing microinjections to determine the influence that sedentary conditions have on the sensitivity of the RVLM. Later, injections of the long-acting GABA agonist muscimol into the right RVLM inhibited the area. The left side continued to receive received microinjections following the same dose-response protocol as before. Lastly, both active and sedentary groups received bilateral sinoaortic denervations (SAD), followed by unilateral GABA microinjections into the left RVLM.
During the intact studies, a dose-dependent response for the MAP and HR were measured following the GABA injections in both active and sedentary animal. However, there was no significant difference between the groups. Upon the inhibition of the right RVLM, there was enhanced sympathoexcitation in sedentary versus active rats. Lastly, there was no difference between the groups in sympathoexcitation when conducted with the SAD animals.
The research successfully demonstrated that there is enhanced GABA sensitivity in the RVLM neurons of sedentary versus active rats. This sensitivity could not be measured, however, until the contralateral RVLM was inhibited and thus prevented from hindering the response from the neurons in the left RVLM. Through these studies, the research helped to support the notion that there is a buffering response between the contralateral RVLM when there are decreases in sympathetic outflow in sedentary rats. With the SAD animals, the lack of a difference between the sedentary and active animals demonstrated that this buffering is not originating from the arterial baroreceptors themselves. Thus, the results suggest that the change is occurring within the central versus peripheral nervous system in sedentary rats.
-O. Flessland
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