Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions

Area of Science:

• Cardiovascular Science
• Pharmacology
• Immunology

Background:

• Low to moderate long-term ethanol consumption shows cardioprotective effects against ischemia-reperfusion (I/R).
• The temporal pattern and underlying mechanisms of ethanol preconditioning (EtOH-PC) against I/R-induced inflammation remain unclear.

Purpose of the Study:

• To investigate the biphasic temporal pattern of EtOH-PC against inflammatory responses to I/R.
• To determine the roles of adenosine and nitric oxide (NO) in initiating the late phase of EtOH-PC.

Main Methods:

• Mice received a single oral ethanol dose, followed by I/R induction at various time points.
• Leukocyte rolling and adhesion in postcapillary venules were quantified using intravital microscopy.
• The involvement of adenosine and NO pathways was assessed using specific inhibitors and agonists.

Main Results:

• EtOH-PC demonstrated early protection (2-3 hours) and a more potent late protection (24 hours) against I/R-induced leukocyte adhesion.
• The late phase protection was abolished by adenosine deaminase or a NO synthase inhibitor.
• Adenosine A(2) receptor agonist preconditioning mimicked late EtOH-PC, and its effect was blocked by NO synthase inhibition.

Conclusions:

• EtOH-PC induces a biphasic protection against the proinflammatory effects of I/R.
• The late phase of EtOH-PC is initiated by NO, which is secondary to adenosine A(2) receptor-dependent activation of NO synthase.