Elevated mitochondrial superoxide contributes to enhanced chemoreflex in heart failure rabbits

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28 Scopus citations

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 × 108 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 ± 1.5 vs. 12.7 ± 1.4 imp/s at ∼100-Torr PO2, P < 0.05) and in response to hypoxia (20.5 ± 1.8 vs. 32.6 ± 1.4 imp/s at ∼40-Torr PO2, P ± 0.05) in CHF rabbits. Compared with Ad Empty, Ad MnSOD reversed the blunted K+ currents in CB glomus cells from CHF rabbits (385 ± 11 vs. 551 ± 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.

Original languageEnglish (US)
Pages (from-to)R303-R311
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Adenoviral vector
  • Carotid body
  • Chronic heart failure
  • Mitochondrial superoxide levels
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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