Sympathetic hyperinnervation in obesity is associated with oxidative stress and inflammatory cell NGF synthesis

Abstract

Obesity is associated with an increased density of the sympathetic nerve plexus over arteries that control blood pressure. Here we examine the role of oxidative stress and inflammatory cell infiltration to changes in perivascular nerve innervation over small mesenteric arteries from C57BL/6 and NOX2−/− mice fed a normal or high fat diet. Changes in smooth muscle membrane potential were measured in response to perivascular nerve stimulation. Innervation density, nerve growth factor (NGF) and inflammatory cell type were examined by immunohistochemistry. Oxidative stress was measured using dihydroethidium fluorescence. Denser nerve plexuses over arteries from obese C57BL/6 mice were associated with larger excitatory junction potentials (EJPs; P<0.05). Oxidative stress and numbers of inflammatory cells positive for NGF were also increased (P<0.05). By contrast, the perivascular nerve plexus in obese NOX2−/− mice was less dense (P<0.05) and EJP amplitude was decreased (P<0.05). Oxidative stress and numbers of NGF positive inflammatory cells were also decreased (P<0.05). We demonstrate that obesity causes an increase in the density of the sympathetic nerve plexus via NOX2dependent and independent processes. Hyperinnervation occurs due to increased oxidative stress and infiltration of NGF producing inflammatory cells. This study was supported by the NHMRC to REH (466009).