Adenoviral CuZnSOD gene transfer to the carotid bodies of heart failure rabbits decreased baseline chemoafferent discharge (7.6 vs 12.6 imp/s) and the response to hypoxia (22.4 vs 32.3 imp/s, P<0.05).
Does adenoviral CuZnSOD gene transfer to the carotid body reduce chemoreceptor activity and chemoreflex function in CHF rabbits?
Downregulation of CuZnSOD in the carotid body contributes to enhanced chemoreceptor activity in heart failure, which can be reversed by CuZnSOD gene transfer in a rabbit model.
Absolute Event Rate: 7.6% vs 12.6%
p-value: p=<0.05
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 approximately 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 approximately 100 mmHg PO2) and the response to hypoxia (22.4 +/- 1.6 vs. 32.3 +/- 1.2 imp/s at approximately 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.
Ding et al. (Thu,) conducted a other in Chronic heart failure (CHF). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer vs. Sham / baseline CHF was evaluated on Baseline discharge from CB chemoafferents and response to hypoxia (p=<0.05). Adenoviral CuZnSOD gene transfer to the carotid bodies of heart failure rabbits decreased baseline chemoafferent discharge (7.6 vs 12.6 imp/s) and the response to hypoxia (22.4 vs 32.3 imp/s, P<0.05).