Acute alcohol intoxication-induced microvascular leakage

Area of Science:

• Physiology
• Cell Biology
• Pharmacology

Background:

• Alcohol intoxication is known to exacerbate inflammation and injury, but the underlying mechanisms remain unclear.
• This study investigates how acute alcohol exposure impacts microvascular permeability and the associated endothelial cell signaling pathways.

Purpose of the Study:

• To determine if acute alcohol intoxication increases microvascular permeability.
• To elucidate the specific endothelial cell signaling mechanisms involved in alcohol-induced barrier dysfunction.

Main Methods:

• Rats received alcohol, and microvascular leakage was assessed using intravital microscopy with FITC-albumin.
• Cultured endothelial cells were used to measure transendothelial electrical resistance (TER) and analyze signaling pathways including p38 MAPK, Rac1, RhoA, and VE-cadherin.

Main Results:

• Alcohol intoxication significantly increased albumin extravasation and decreased TER in the mesenteric microcirculation.
• Alcohol disrupted VE-cadherin localization and activated p38 MAPK and Rac1, contributing to barrier dysfunction.
• While acetaldehyde also decreased TER, only p38 MAPK inhibition attenuated alcohol-induced barrier dysfunction.

Conclusions:

• Alcohol intoxication increases microvascular permeability to plasma proteins.
• Endothelial barrier dysfunction is mediated by p38 MAPK, Rac1, and VE-cadherin reorganization.
• Exchange protein activated by cAMP (Epac) activation can rapidly reverse alcohol-induced endothelial barrier dysfunction.