Exercise training reduces brainstem oxidative stress and restores normal breathing function in heart failure

Area of Science:

• Cardiovascular Physiology
• Respiratory Control
• Neuroscience

Background:

• Heart failure (HF) is characterized by enhanced central chemoreflex drive and irregular breathing, impacting disease progression.
• The retrotrapezoid nucleus (RTN) plays a crucial role in breathing alterations observed in HF.
• Exercise (EX) has shown potential in reducing reactive oxygen species (ROS) in HF models, but its specific effect on the RTN and breathing control in HF remains unclear.

Purpose of the Study:

• To investigate ROS levels in the RTN of HF rats and their association with enhanced chemoreflex drive and breathing disorders.
• To determine if EX training can ameliorate chemoreflex and breathing dysfunction in HF by reducing RTN ROS levels.
• To identify molecular changes related to ROS generation in the RTN of HF rats and assess the impact of EX on these pathways.

Main Methods:

• Adult male Sprague-Dawley rats were assigned to Sham, HF, or HF with EX groups.
• HF was induced via volume overload. The EX group underwent 6 weeks of treadmill training.
• Breathing patterns and chemoreflex function were assessed using unrestrained plethysmography. RTN ROS levels and antioxidant/pro-oxidant gene expression were analyzed.

Main Results:

• HF rats exhibited elevated ROS levels in the RTN, strongly correlated with enhanced central chemoreflex and irregular breathing.
• HF rats showed decreased expression of antioxidant genes in the RTN compared to controls.
• EX training significantly increased antioxidant defense in the RTN, reduced ROS production, and restored normal chemoreflex drive and breathing regularity in HF rats.

Conclusions:

• Elevated ROS in the RTN contribute to central chemoreception dysfunction and breathing abnormalities in heart failure.
• Exercise training effectively mitigates ROS in the brainstem RTN, thereby normalizing chemoreflex and breathing patterns in HF.
• Targeting ROS in the RTN via exercise presents a promising therapeutic strategy for managing respiratory complications in heart failure.