Exercise evokes sympathetic activation and increases blood pressure and heart rate. Two neural mechanisms that cause the exercise-induced increase in sympathetic discharge are central command and the exercise pressor reflex (EPR). The former suggests that a volitional signal emanating from central motor areas leads to increased sympathetic activation during exercise. The latter is a peripheral neural reflex originating in skeletal muscle which contributes significantly to the regulation of the cardiovascular and respiratory systems during exercise. In heart failure, the sympathetic activation during exercise is exaggerated, which potentially increases cardiovascular risk and contributes to exercise intolerance during physical activity in chronic heart failure (CHF) patients. Our work focuses primarily on the neural control mechanisms underlying the exaggerated cardiovascular response and hyperventilation during exercise in the CHF state. We recently provided the direct evidence demonstrating that muscle mechanically sensitive afferents (Group III) are sensitized in a CHF rat model whereas the metabolically sensitive afferents (group IV) are desensitized. Currently, our study is looking for the cellular and molecular mechanisms underlying the abnormal sensitization of muscle afferents in CHF with the integrative techniques such as patch clamp, single fiber recording and common molecular techniques (western blot, PCR, immunohistochemistry and in vivo or in vitro gene transfer). In addition, we recently found that besides muscle afferents, spinal cord dysfunction may also contribute to the exaggerated cardiovascular response during exercise in CHF. The imbalance between glutamatergic and GABAergic input in the spinal cord may cause the enhanced spinal neuronal excitability in CHF. Finally, based on our previous finding that long-term exercise training (ExT), as a non-pharmacological therapeutic strategy, prevents the progression of the exaggerated EPR in CHF. We are focusing on the underlying mechanisms.
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