Microvascular Dysfunction with Increased Vascular Leakage Response in Mice Systemically Exposed to Arsenic

作者：Chen Shih Chieh^*; Huang Shin Yin; Lu Chi Yu; Hsu Ya Hung; Wang Dean Chuan

来源：Cardiovascular Toxicology, 2014, 14(3): 222-231.

DOI：10.1007/s12012-014-9246-2

• Arsenic
• Type-2 protein phosphatase
• Sodium arsenite
• Vascular leakage
• Neurokinin 1 receptor
• Microvascular dysfunction

The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

• 出版日期2014-9
• 单位河北医科大学