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

Area of Science:

• Cardiovascular Physiology
• Neuroscience
• Autonomic Nervous System Regulation

Background:

• Central command, a brain-driven activation of motor and autonomic systems, is exaggerated in chronic heart failure (CHF).
• The role of medullary oxidative stress in this exaggerated sympathoexcitation and the effects of exercise training remain unclear.

Purpose of the Study:

• To investigate if medullary oxidative stress contributes to exaggerated central command sympathoexcitation in CHF.
• To determine if exercise training in CHF reduces central command sympathoexcitation via antioxidant mechanisms in the medulla.

Main Methods:

• Used decerebrate rats with myocardial infarction (MI)-induced CHF and sham-operated controls.
• Activated central command via mesencephalic locomotor region (MLR) stimulation.
• Administered superoxide dismutase (SOD) mimetics (Tempol, Tiron) into the rostral ventrolateral medulla (RVLM) and assessed renal sympathetic nerve activity and arterial pressure.

Main Results:

• MLR stimulation caused greater sympathoexcitation in CHF rats compared to controls and exercise-trained CHF rats.
• RVLM administration of SOD mimetics attenuated sympathoexcitation in CHF rats but not controls.
• Enhanced superoxide generation was observed in the RVLM of CHF rats, which was reduced by exercise training.

Conclusions:

• Oxidative stress in the medulla mediates exaggerated central command sympathoexcitation in CHF.
• Exercise training normalizes central command dysfunction in CHF through antioxidant effects in the medulla.