In vivo transfection of manganese superoxide dismutase gene or nuclear factor ?B shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats.

ABSTRACT: Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased expression and activation of the sodium channels in the baroreceptor neurons from CHF rats. However, the molecular mechanisms responsible for the sodium channel dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested the involvement of nuclear factor ?B (NF?B) in the sodium channel dysfunction and evaluated the effects of in vivo transfection of manganese superoxide dismutase gene and NF?B shRNA on the baroreflex function in CHF rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in adult rats. Western blot and chromatin immunoprecipitation data showed that phosphorylated NF?B p65 and ability of NF?B p65 binding to the sodium channel promoter were increased in the nodose ganglia from CHF rats. In vivo transfection of adenoviral manganese superoxide dismutase gene or lentiviral NF?B p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium channel expression and cell excitability in the baroreceptor neurons and improved CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of adenoviral manganese superoxide dismutase also inhibited the augmentation of phosphorylated NF?B p65 in the nodose neurons from CHF rats. The present study suggests that superoxide-NF?B signaling contributes to CHF-induced baroreceptor dysfunction and resultant impairment of baroreflex function.

SUBMITTER: Zhang D 

PROVIDER: S-EPMC3893036 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature