Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits

Area of Science:

• Cardiovascular Physiology
• Mitochondrial Biology
• Neuroscience

Background:

• Peripheral chemoreflex sensitivity is heightened in chronic heart failure (CHF).
• The carotid body (CB) plays a crucial role in regulating chemoreflex responses.
• Mitochondrial dysfunction, specifically involving superoxide levels, is implicated in enhanced CB activity in CHF.

Purpose of the Study:

• To investigate the role of manganese superoxide dismutase (MnSOD) and mitochondrial superoxide levels in the carotid body (CB) of rabbits with CHF.
• To determine if restoring MnSOD levels can normalize CB function and chemoreflex activity in CHF.

Main Methods:

• Utilized a rabbit model of chronic heart failure (CHF).
• Measured MnSOD protein expression and mitochondrial superoxide levels in the carotid body (CB).
• Employed adenovirus-mediated gene transfer (Ad MnSOD) to selectively increase MnSOD expression in the CB.
• Assessed renal sympathetic nerve activity, single-fiber discharge from CB chemoreceptors, and K+ currents in CB glomus cells.

Main Results:

• CHF rabbits exhibited suppressed MnSOD expression and elevated mitochondrial superoxide levels in the CB.
• Ad MnSOD gene transfer normalized mitochondrial superoxide levels and increased MnSOD expression in CHF CBs.
• Ad MnSOD treatment normalized baseline and hypoxia-evoked renal sympathetic nerve activity in CHF rabbits.
• Ad MnSOD reversed the enhanced baseline and hypoxia-evoked chemoreceptor nerve activity and blunted K+ currents in CHF CB glomus cells.

Conclusions:

• Decreased MnSOD in the carotid body (CB) and elevated mitochondrial superoxide contribute to enhanced CB chemoreceptor activity in chronic heart failure (CHF).
• Restoring MnSOD levels via gene transfer can normalize mitochondrial function and correct the enhanced peripheral chemoreflex in CHF.