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Norepinephrine (NE) concentrations in exercising muscle with myocardial infarction: Implications for cardiovascular regulation in heart failure (HF)
Author(s) -
Li Jianhua,
Gao Zhaohui,
Kehoe Valerie,
King Nicholas,
Rice Kristen,
Sinoway Lawrence I.
Publication year - 2006
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.20.4.a770-b
Subject(s) - medicine , skeletal muscle , contraction (grammar) , stimulation , endocrinology , cardiology , heart failure , myocardial infarction , vasoconstriction , contractility , vasodilation
Skeletal muscle NE rises with exercise. In HF this response is augmented evoking vasoconstriction, reduced muscle blood flow and exercise intolerance. In this study, we examine interstitial K + concentrations ([K + ]i) during muscle contractions in control rats and rats with myocardial infarction (MI). MI leads to LV dysfunction and HF. We hypothesized that the rate of rise in [K + ]i with contraction would be greater in MI than in controls and this would evoke a larger increase in [NE]i (index of neurovascular NE). Contraction was induced by electrical stimulation of the sciatic nerve of 6 control and 6 MI rats. Dialysis probes were inserted in the muscle and the ends of the probes were attached to K + electrodes to measure [K + ]i. Dialysate [NE] was determined by the HPLC. Stimulation at 1 and 3 Hz increased muscle [K + ]i by 9% and 51% in controls, and by 18% and 75% in MI rats ( P <0.05 vs. control), respectively. Ouabain, an inhibitor of Na + ‐K + pump significantly elevated [K + ]i at rest and this effect was attenuated in MI. In addition, 10 mM of KCl added to the perfusate increased [NE]i. An uptake 1 inhibitor desipramine (1.0 μmol/L) was injected into the muscle in 5 controls and in 4 MI rats. This increased [NE]i by 23% in control and 5% ( P <0.05 vs. control) in MI. In conclusion, as compared with controls, exercising muscle [K + ]i is augmented in HF. This is due to attenuated Na + ‐K + pump. This factor in addition to impaired uptake 1 contributes to the augmented muscle NEi seen in HF with exercise. Support: NIH R01 HL075533 (Li), R01 HL078866 (Li), R01 HL060800 (Sinoway).