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J Physiol. 2014 Sep 1;592(17):3917-31. doi: 10.1113/jphysiol.2014.272377. Epub 2014 Jun 27.

Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

Author information

1
Division of Integrative Physiology, Faculty of Medicine, Tottori University, Yonago, Japan skoba@med.tottori-u.ac.jp.
2
Division of Regenerative Medicine and Therapeutics, Graduate School of Medical Science, Tottori University, Yonago, Japan.
3
Division of Integrative Physiology, Faculty of Medicine, Tottori University, Yonago, Japan.

Abstract

Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

PMID:
24973409
PMCID:
PMC4192711
DOI:
10.1113/jphysiol.2014.272377
[Indexed for MEDLINE]
Free PMC Article

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