1. Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits
- Author
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Ding, Yanfeng, Li, Yu-Long, Zimmerman, Matthew C., and Schultz, Harold D.
- Subjects
Chemoreceptors -- Physiological aspects ,Chemoreceptors -- Research ,Heart failure -- Risk factors ,Heart failure -- Research ,Mitochondrial DNA -- Physiological aspects ,Mitochondrial DNA -- Research ,Superoxide dismutase -- Measurement ,Superoxide dismutase -- Physiological aspects ,Superoxide dismutase -- Research ,Biological sciences - Abstract
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.sup.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 ~100-Tort [Po.sub.2], P < 0.05) and in response to hypoxia (20.5 [+ or -] 1.8 vs. 32.6 [+ or -] 1.4 imp/s at ~40-Torr [Po.sub.2], P < 0.05) in CHF rabbits. Compared with Ad Empty, Ad MnSOD reversed the blunted [K.sup.+] 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. superoxide dismutase; mitochondrial superoxide levels; adenoviral vector; carotid body; chronic heart failure doi: 10.1152/ajpregu.00629.2009
- Published
- 2010