Adenovirus‐mediated gene transfer of Mn superoxide dismutase to carotid body normalizes enhanced chemoreceptor function in heart failure rabbits

Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). We have found CuZn superoxide dismutase (SOD) gene transfer to the carotid body (CB) and tempol (an SOD mimetic) reverse the enhanced chemoreceptor function in heart failure rabbits. Here we investigated the role of MnSOD in the enhanced chemoreceptor activity and function of the CB in CHF rabbits. MnSOD protein expression was lower in CHF CB compared with that in sham CBs. Ad MnSOD (1x10 8 pfu/ml) gene transfer to the CBs significantly increased MnSOD expression in CHF CBs and reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits. Ad MnSOD decreased the baseline single‐fiber discharge from CB chemoreceptors (6.4± 1.3 vs.10.5±0.9 imp/s at ~100 mm Hg PO 2 ) and the response to hypoxia (18.4±2.1 vs. 36.7±2.2 imp/s at ~40 mm Hg PO 2 , p<0.05) in CHF rabbits. In addition, Ad MnSOD normalized the blunted IK in CB glomus cells from CHF rabbits (362±41 vs. 520±65 pA/pF at +70 mV, p<0.05). Ad MnSOD also normalized the blunted IK induced by angiotensin II in CB glomus cells from sham rabbits. These results suggest that decreased MnSOD in the CB may contribute to the enhanced CB chemoreceptors activity and peripheral chemoreflex function in CHF rabbits. Supported by NIH grant PO‐1 HL 62222