(In)activity dependent alterations in RVLM control of splanchnic sympathetic nerve activity

Physical inactivity contributes to the development of cardiovascular disease (CVD). In humans and animals physical activity can reduce sympathetic nervous system overactivity, a component of CVD. Past work has shown that sedentary animals have increased responses to stimulation of the rostral ventrolateral medulla (RVLM). Since enhanced splanchnic sympathetic nerve activity (sSNA) has been implicated in models of hypertension, we hypothesized that sedentary conditions could produce changes in RVLM neurons resulting in hyperresponsive sSNA. Inactin anesthetized sedentary (n=5) or physically active (n=4) rats were instrumented to record arterial pressure (AP) and sSNA responses to microinjections of glutamate (1–100mM, 30nl) in the RVLM. Raw nerve activity was rectified, integrated, and amplified similarly in each animal. Sedentary animals exhibited a trend for increased sSNA responses to the highest dose of glutamate (Δ1.06 ± 0.15 vs. Δ0.63 ± 0.18 a.u., p=0.052). After ganglionic blockade (hexamethonium, 30 mg/kg, i.v.), vascular responses to phenylephrine (PE, 0.25–20 μg/kg, i.v.) were tested in both groups (n=6 each). Sedentary animals exhibited trends for increased AP responses at the higher doses of PE (p=0.07). These data suggest that RVLM neurons and the vasculature in sedentary animals are altered in ways which contribute to SNS overactivity and hypertension.(F30HL105003 R01HL096787)