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

Yanfeng Ding, Yulong Li, Matthew C Zimmerman, Robin L. Davisson, Harold D Schultz

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 ∼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 ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼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.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalCardiovascular research
Volume81
Issue number4
DOIs
StatePublished - Mar 1 2009

Fingerprint

Carotid Body
Superoxide Dismutase
Heart Failure
Rabbits
Superoxides
Angiotensin II
Kidney
NADPH Oxidase
Proteins
Down-Regulation

Keywords

  • Adenoviral vector
  • Carotid body
  • Chemoreceptor
  • Chronic heart failure
  • Glomus cell
  • Superoxide dismutase
  • Sympathetic nerve activity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Role of CuZn superoxide dismutase on carotid body function in heart failure rabbits. / Ding, Yanfeng; Li, Yulong; Zimmerman, Matthew C; Davisson, Robin L.; Schultz, Harold D.

In: Cardiovascular research, Vol. 81, No. 4, 01.03.2009, p. 678-685.

Research output: Contribution to journalArticle

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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 ∼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 ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼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.",
keywords = "Adenoviral vector, Carotid body, Chemoreceptor, Chronic heart failure, Glomus cell, Superoxide dismutase, Sympathetic nerve activity",
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T1 - Role of CuZn superoxide dismutase on carotid body function in heart failure rabbits

AU - Ding, Yanfeng

AU - Li, Yulong

AU - Zimmerman, Matthew C

AU - Davisson, Robin L.

AU - Schultz, Harold D

PY - 2009/3/1

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N2 - 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 ∼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 ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼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.

AB - 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 ∼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 ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼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.

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KW - Glomus cell

KW - Superoxide dismutase

KW - Sympathetic nerve activity

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