Background and Objective:
The risk of developing hypertension is increased in individuals who are overweight or obese. Obesity is associated with oxidative stress, chronic low grade inflammation and increased sympathetic outflow. The direct link between oxidative stress and changes in the perivascular sympathetic nerve plexus during hypertension in the obese remains unexplored.
Design and methods:
C57BL/6 and NOX2-/- mice were fed a normal or high fat diet for 10 weeks. Mesenteric arteries were isolated, inflammatory cell recruitment was determined using FACS analysis, and tissue sections were stained with haemotoxylin and eosin. Immunohistochemistry was performed using antibodies against synaptic vesicles, tyrosine hydroxylase and nerve growth factor (NGF). Confocal microscopy was used to examine arterial perivascular sympathetic nerve density and arterial NGF expression. Oxidative stress was measured using dihydroethidium fluorescence.
Results:
In C57BL/6 mice, obesity was associated with increased oxidative stress in perivascular sympathetic nerves and increased numbers of adventitial inflammatory cells expressing NGF (P<0.05). The density of the sympathetic nerve plexus was also higher in arteries from obese animals (P<0.05). By contrast, arteries from NOX2-/- mice exhibited lower levels of oxidative stress and sympathetic innervation (P<0.05). Similar numbers of perivascular inflammatory cells were present in C57BL/6 and NOX2-/-.
Conclusions:
Obesity causes an increase in the density of the perivascular sympathetic nerve plexus over mesenteric arteries. These changes appear to occur at least in part due to increased oxidative stress within sympathetic nerve fibres, and increased inflammatory cell infiltration and production of NGF.