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Exercise training improves peripheral chemoreflex function in heart failure rabbits.

Yu-Long Li1, Yanfeng Ding, Chad Agnew

  • 1Dept. of Cellular and Integrative Physiology, Univ. of Nebraska Medical Center, Omaha, NE 68198, USA.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|June 28, 2008
PubMed
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Exercise training partially normalizes sympathetic hyperactivity in chronic heart failure (CHF) by improving carotid body (CB) chemoreceptor function. This involves restoring pathways related to nitric oxide (NO) and angiotensin II (ANG II).

Area of Science:

  • Cardiovascular Physiology
  • Neuroscience
  • Exercise Physiology

Background:

  • Peripheral chemoreflex sensitivity is enhanced in chronic heart failure (CHF), contributing to sympathetic hyperactivity.
  • This enhanced chemoreflex involves augmented carotid body (CB) activity due to angiotensin II (ANG II) type 1 receptor pathway upregulation and neuronal nitric oxide synthase (nNOS)-nitric oxide (NO) pathway downregulation in the CB.
  • Sympathetic hyperactivity in CHF exacerbates the condition and is linked to increased cardiovascular risk.

Purpose of the Study:

  • To investigate whether exercise training (EXT) can normalize the enhanced peripheral chemoreflex function in CHF rabbits.
  • To elucidate the underlying mechanisms by which EXT might affect the CB chemoreceptor pathways in CHF.

Main Methods:

  • Chronic heart failure (CHF) was induced in rabbits.

Related Experiment Videos

  • Exercise training (EXT) was implemented in a subset of CHF rabbits.
  • Renal sympathetic nerve activity (RSNA) was measured.
  • CB nerve single-fiber discharge was recorded.
  • Carotid bodies were analyzed for ANG II and nNOS expression and NO concentration.
  • Pharmacological interventions (ANG II, nNOS inhibitor) were used to probe CB function.

    • Main Results:

    • EXT partially normalized exaggerated baseline RSNA and the RSNA response to hypoxia in CHF rabbits.
    • EXT reduced baseline CB nerve discharge and the response to hypoxia in CHF rabbits, effects reversible by ANG II or nNOS inhibition.
    • EXT increased NO concentration and nNOS protein expression in the CBs of CHF rabbits, while blunting elevated ANG II and AT(1)-receptor overexpression.

    Conclusions:

    • Exercise training normalizes carotid body (CB) chemoreflex in chronic heart failure (CHF) by preventing increased afferent CB chemoreceptor activity.
    • EXT reverses alterations in the nNOS-NO and ANG II-AT(1)-receptor pathways within the CB that are responsible for chemoreceptor sensitization in CHF.
    • These findings suggest that exercise training is a potential therapeutic strategy to mitigate sympathetic hyperactivity in CHF.