Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic

Area of Science:

• Environmental toxicology
• Cardiovascular physiology
• Biochemistry

Background:

• Cardiovascular disease mechanisms from arsenic exposure remain unclear.
• Vascular leakage is a key factor in cardiovascular pathology.
• Type-2 protein phosphatase (PP2A) role in vascular function needs further investigation.

Purpose of the Study:

• To determine if arsenic exposure increases vascular leakage response to vasoactive agents.
• To investigate the involvement of enhanced PP2A activity in mustard oil-induced vascular leakage.

Main Methods:

• ICR mice were fed sodium arsenite or water for 4 or 8 weeks.
• Vascular leakage was assessed using Evans blue and carbon particle labeling.
• PP2A activity, protein levels, and neurokinin 1 receptor (NK1R) blockade effects were analyzed.

Main Results:

• Arsenic-fed mice showed increased vascular leakage (Evans blue, carbon particles) after mustard oil or histamine administration.
• PP2A activity was significantly higher in arsenic-fed mice.
• PP2A and NK1R inhibitor pretreatment reduced mustard oil-induced leakage in arsenic-fed mice.

Conclusions:

• Arsenic exposure enhances microvascular response to vasoactive agents.
• Increased PP2A activity is implicated in arsenic-induced vascular leakage.
• Arsenic may cause endothelial dysfunction, leading to increased vascular permeability.