(In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nervous activity

By Nicholas A. Mischel and Patrick J. Mueller

Journal of Applied Physiology, October 2011

Sympathetic motor neurons stemming from the RVLM are directly regulated by excitatory (glutamate) and inhibitory (GABA) neurotransmitters. Based on previous studies from the Mischel/Mueller lab, it has become clear that is possible that chronic physical inactivity affects the excitability of RVLM neurons directly and contributes to sympathetic over activity and increased risk of cardiovascular disease in sedentary individuals. The purpose of this study is to test the hypothesis that chronic physical inactivity leads to augmented resting and reflex-mediated splanchnic sympathetic nerve activity (SSNA), resting blood pressure, and vascular reactivity.

To address this hypothesis, rats were housed in the lab for 10-13 weeks under experimental conditions. During this time they were randomly split into two groups: active (running wheel in cage, n=16) and inactive (no running wheel, n=17). After the 10-13 week period, the rats were anesthetized and mean arterial pressure (MAP) and SSNA were recorded from the rats. Next, the rats' responses to RVLM microinjections of glutamate, baroreceptor unloading (sodium nitroprusside), and vascular reactivity (preformed under autonomic blockade with Phenylephrine) were measured. In order to record this data, catheters were inserted into the femoral artery and vein of the rats. The catheters were used for recordings of MAP, as well as administration of drugs. Along with the catheters, an electrode was placed on the splanchnic sympathetic nerve to record SSNA in response to the various experimental conditions.

Sedentary animals exhibited increased resting SSNA and MAP, increases in SSNA in response to RVLM activation and baroreceptor unloading, and increased vascular reactivity to alpha 1-mediated vasoconstriction. It is thought that the augmented response of the sedentary RVLM to glutamate, whether through direct activation or baroreceptor unloading, is one of the mechanisms through which sedentary conditions lead to increased sympathoexcitation. In addition, these data showed that the vasculature of sedentary animals is more apt to vasoconstrict in response to stimulation.  These results suggest that a sedentary lifestyle increases the risk of cardiovascular disease by augmenting resting and reflex-mediated sympathetic output to the splanchnic circulation and also by increasing vascular sensitivity to adrenergic stimulation.

- Ben Huber