Adenovirus MnSOD gene transfer to the carotid bodies decreased baseline single-fiber discharge from chemoreceptors compared with Ad Empty (6.3 vs. 12.7 imp/s, P<0.05) in CHF rabbits.
Decreased MnSOD and elevated mitochondrial superoxide in the carotid body contribute to enhanced chemoreflex function in heart failure, which can be reversed by MnSOD gene transfer in a rabbit model.
Absolute Event Rate: 6.3% vs 12.7%
p-value: p=<0.05
Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). Here we investigated the role of manganese superoxide dismutase (MnSOD), the SOD isoform specially targeted to mitochondria, and mitochondrial superoxide levels in the enhanced chemoreceptor activity and function of the carotid body (CB) in CHF rabbits. CHF suppressed MnSOD protein expression and elevated mitochondrial superoxide levels in CB compared with that in sham CB. Adenovirus (Ad) MnSOD (1 x 10(8) plaque-forming units/ml) gene transfer selectively to the CBs normalized mitochondrial superoxide levels in glomus cells from CHF CB. In addition, Ad MnSOD reduced the elevation of superoxide level in CB tissue from CHF rabbits. Ad MnSOD significantly increased MnSOD expression in CHF CBs and normalized the baseline renal sympathetic nerve activity and the response of renal sympathetic nerve activity to hypoxia in CHF rabbits. Ad MnSOD decreased baseline single-fiber discharge from CB chemoreceptors compared with Ad Empty (6.3 + or - 1.5 vs. 12.7 + or - 1.4 imp/s at approximately 100-Torr Po(2), P < 0.05) and in response to hypoxia (20.5 + or - 1.8 vs. 32.6 + or - 1.4 imp/s at approximately 40-Torr Po(2), P < 0.05) in CHF rabbits. Compared with Ad Empty, Ad MnSOD reversed the blunted K(+) currents in CB glomus cells from CHF rabbits (385 + or - 11 vs. 551 + or - 20 pA/pF at +70 mV, P < 0.05). The results suggest that decreased MnSOD in the CB and elevated mitochondrial superoxide levels contribute to the enhanced CB chemoreceptor activity and peripheral chemoreflex function in CHF rabbits.
Ding et al. (Wed,) conducted a other in Chronic heart failure (CHF). Adenovirus (Ad) MnSOD gene transfer vs. Ad Empty was evaluated on Baseline single-fiber discharge from carotid body chemoreceptors (imp/s) (p=<0.05). Adenovirus MnSOD gene transfer to the carotid bodies decreased baseline single-fiber discharge from chemoreceptors compared with Ad Empty (6.3 vs. 12.7 imp/s, P<0.05) in CHF rabbits.