Role of CuZn superoxide dismutase on carotid body function in heart failure rabbits

Cardiovasc Res. 2009 Mar 1;81(4):678-85. doi: 10.1093/cvr/cvn350. Epub 2008 Dec 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Adenoviridae / genetics
  • Animals
  • Blotting, Western
  • Carotid Body / enzymology*
  • Carotid Body / physiopathology
  • Chronic Disease
  • Disease Models, Animal
  • Electric Capacitance
  • Fluorescent Antibody Technique
  • Gene Transfer Techniques
  • Genetic Vectors
  • Heart Failure / enzymology*
  • Heart Failure / physiopathology
  • Humans
  • Hypoxia / enzymology
  • Hypoxia / physiopathology
  • Kidney / innervation*
  • Male
  • Potassium / metabolism
  • Rabbits
  • Reflex*
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Superoxides / metabolism
  • Sympathetic Nervous System / physiopathology*

Substances

  • SOD1 protein, human
  • Superoxides
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Potassium