In‐vivo transfection of manganese SOD gene and NFkB shRNA into nodose ganglia improve blunted baroreflex sensitivity in chronic heart failure rats

Abstract

Blunted baroreflex sensitivity is observed in chronic heart failure (CHF) patients and animals. Our previous study has shown that mitochondria‐derived superoxide‐NFκB signaling reduces the Nav channel activation in baroreceptor neurons. Additionally, reduced Nav channel activiation contributes to the impairment of baroreflex sensitivity in the CHF state. Using in‐vivo gene transfection technique in present study, we examined the effect of Adenoviral Manganese SOD (Ad.MnSOD) and lentiviral NFκB p65 shRNA on the attenuated baroreflex function in CHF rats. CHF were induced by left coronary ligation. CHF significantly elevated mitochondrial superoxide and NFκB p65 expression in nodose neurons, and blunted baroreflex sensitivity. Ad.MnSOD transfection (4×107 PFU) into the nodose ganglia (NG) decreased CHF‐enhanced mitochondrial superoxide and NFκB p65 expression in nodose neurons, and improved baroreflex sensitivity in CHF rats. Similarly local transfection of lentivial NF‐κB p65 shRNA (5×103 IFU) into the NG also improved baroreflex sensitivity in CHF rats. These results suggest that mitochondrial superoxide‐NFκB signaling is involved in the impairment of baroreflex function in CHF rats.