Exercise training improves peripheral chemoreflex function in heart failure rabbits

Yu Long Li, Yanfeng Ding, Chad Agnew, Harold D. Schultz

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


An enhancement of peripheral chemoreflex sensitivity contributes to sympathetic hyperactivity in chronic heart failure (CHF) rabbits. The enhanced chemoreflex function in CHF involves augmented carotid body (CB) chemoreceptor activity via upregulation of the angiotensin II (ANG II) type 1 (AT 1)-receptor pathway and downregulation of the neuronal nitric oxide synthase (nNOS)-nitric oxide (NO) pathway in the CB. Here we investigated whether exercise training (EXT) normalizes the enhanced peripheral chemoreflex function in CHF rabbits and possible mechanisms mediating this effect. EXT partially, but not fully, normalized the exaggerated baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits. EXT also decreased the baseline CB nerve single-fiber discharge (4.9 ± 0.4 vs. 7.7 ± 0.4 imp/s at PO2 = 103 ± 2.3 Torr) and the response to hypoxia (20.6 ± 1.1 vs. 36.3 ± 1.3 imp/s at PO 2 ± 41 ± 2.2 Torr) from CB chemoreceptors in CHF rabbits, which could be reversed by treatment of the CB with ANG II or a nNOS inhibitor. Our results also showed that NO concentration and protein expression of nNOS were increased in the CBs from EXT + CHF rabbits, compared with that in CHF rabbits. On the other hand, elevated ANG II concentration and AT 1-receptor overexpression of the CBs in CHF state were blunted by EXT. These results indicate that EXT normalizes the CB chemoreflex in CHF by preventing an increase in afferent CB chemoreceptor activity. EXT reverses the alterations in the nNOS-NO and ANG II-AT1-receptor pathways in the CB responsible for chemoreceptor sensitization in CHF.

Original languageEnglish (US)
Pages (from-to)782-790
Number of pages9
JournalJournal of Applied Physiology
Issue number3
StatePublished - Sep 2008


  • Angiotensin
  • Carotid body
  • Chemoreceptor
  • Heart failure
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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