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1.  Role of CuZn superoxide dismutase on carotid body function in heart failure rabbits 
Cardiovascular Research  2008;81(4):678-685.
Aims
Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this Ang II- and CHF-enhanced superoxide anion effect. Here we investigated the role of cytoplasmic SOD [CuZn superoxide dismutase (CuZnSOD)] in the CB on chemoreceptor activity and function in CHF rabbits.
Methods and results
CuZnSOD protein expression was decreased in CBs from CHF rabbits vs. sham (P < 0.05). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer to the CBs increased CuZnSOD protein expression and significantly reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits (P < 0.05). Single-fibre discharge from CB chemoafferents during normoxia (baseline, at ∼100 mmHg PO2) and in response to hypoxia were enhanced in CHF vs. sham rabbits (P < 0.05). Ad CuZnSOD decreased the baseline discharge (7.6 ± 1.3 vs. 12.6 ± 1.7 imp/s at ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼40 mmHg PO2, P < 0.05) in CHF rabbits. Ad CuZnSOD also normalized the blunted outward K+ current (IK) in CB glomus cells from CHF rabbits (369 ± 14 vs. 565 ± 31 pA/pF at +70 mV, P < 0.05). In addition, Ad CuZnSOD reduced the elevation of superoxide level in CBs from CHF rabbits.
Conclusion
Downregulation of CuZnSOD in the CB contributes to the enhanced activity of CB chemoreceptors and chemoreflex function in CHF rabbits.
doi:10.1093/cvr/cvn350
PMCID: PMC2642603  PMID: 19091790
Superoxide dismutase; Adenoviral vector; Carotid body; Sympathetic nerve activity; Chemoreceptor; Glomus cell; Chronic heart failure

Results 1-1 (1)