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Skeletal muscle superoxide is involved in the enhanced exercise pressor reflex in heart failure rats
Author(s) -
Pan YanXia,
Wang WeiZhong,
Fahim Mohammad,
Zucker Irving H,
Wang Wei
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a570-b
Subject(s) - medicine , skeletal muscle , superoxide , endocrinology , reflex , hindlimb , denervation , superoxide dismutase , stimulation , heart failure , baroreceptor , chemistry , anesthesia , oxidative stress , heart rate , blood pressure , biochemistry , enzyme
The augmented exercise pressor reflex (EPR) in chronic heart failure (CHF) is associated with sensitization of muscle afferents to metabolite stimulation. Superoxide is increased in exercising skeletal muscle, however it is unknown if the increased superoxide enhances the EPR. We hypothesized that superoxide in skeletal muscle modulates the EPR. Four to six weeks after myocardial infarction, CHF was confirmed by a significant fall in ejection fraction compared with sham rats (49.2 ± 2.8 % vs. 84.2 ± 2.4 %, P<0.05, n=5 for each group). In anaesthetized rats with sino‐aortic denervation and cervical vagotomy, muscle contraction elicited by electrical stimulation of L4 or L5 ventral roots produced larger pressor responses in CHF rats compared to sham rats (20.8 ± 2.5 mmHg vs.12.2 ± 1.4 mmHg, P<0.05). Injection of the superoxide dismutase (SOD) inhibitor DETC (10mg/kg, 0.1ml) into the artery supplying the hindlimb significantly enhanced the pressor response in sham rats (17.4 ± 0.6mmHg vs.12.2 ± 1.4 mmHg, P<0.05), but not in CHF rats. Administration of the SOD mimetic tempol (10mg/kg, 0.1ml, i.a.) decreased the pressor response in sham rats (6.6 ± 0.7 mmHg vs.11.8 ± 1.9 mmHg) and CHF rats (7.8 ± 1.0 mmHg vs.18.4 ± 2.3 mmHg), P<0.05 for both groups. The results suggest that superoxide produced by contracting muscle modulates the EPR and may contribute to the enhanced EPR in the CHF state. Supported by NIH grant PO‐1 HL 62222.