Acetylcholinesterase inhibition affects cardiovascular structure in mice

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Stress Physiology

Background:

• Acetylcholinesterase (AChE) inhibitors like pyridostigmine bromide (PB) are used clinically.
• The combined effects of PB and stress on cardiovascular health are not fully understood.
• Understanding these interactions is crucial for assessing potential risks.

Purpose of the Study:

• To investigate the impact of continuous pyridostigmine bromide (PB) exposure and shaker stress on cardiovascular function, structure, and apoptosis in male C57BL/6J mice.
• To determine if stress modulates the cardiovascular effects of PB.
• To assess cardiac and vascular cellular apoptosis.

Main Methods:

• Male C57BL/6J mice were treated for seven days with PB (10 mg/kg/day), shaker stress, or a combination.
• Cardiovascular parameters including mean arterial pressure (MAP) and heart rate (HR) were monitored.
• Aortic wall thickness, relative heart weight, and apoptosis markers (Bax, Bcl-2) were analyzed using immunochemistry.

Main Results:

• PB significantly reduced AChE activity but did not alter 24-h MAP or HR.
• Stress increased MAP and HR in both Stress and PB+Stress groups.
• PB treatment reduced aortic wall thickness/diameter ratio and relative heart weight, effects blunted by stress.
• PB increased the Bax/Bcl-2 ratio in the heart, indicating apoptosis, while attenuating it in the aortic endothelium.

Conclusions:

• Short-term, continuous PB exposure can adversely affect cardiac and vascular structure and promote heart cell apoptosis, irrespective of MAP and HR.
• Simultaneous stress exposure partially mitigated some structural vascular effects of PB.
• The findings highlight potential cardiovascular risks associated with PB, even without significant hemodynamic changes.