Norepinephrine (NE) concentrations in exercising muscle with myocardial infarction: Implications for cardiovascular regulation in heart failure (HF)

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).