Antecedent ethanol ingestion prevents postischemic microvascular dysfunction.

Abstract

Prolonged ischemia followed by reperfusion (I/R) results in impaired endothelial cell function in all segments of the microvasculature. Moreover, microcirculatory dysfunction plays a major role in the genesis of the reperfusion component of total tissue injury in I/R. Thus, preservation of endothelial function is an important therapeutic goal for ameliorating injury in tissues subjected to I/R. An accumulating body of evidence indicates that low to moderate ethanol consumption produces an adaptive transformation to a protected phenotype in both microvascular endothelium and parenchymal cells such that they are rendered resistant to the pathologic effects of I/R. The purpose of this review is to summarize our current understanding of the signaling pathways underlying the development of the preconditioned state induced by antecedent ethanol in arteriolar, capillary, and venular endothelium. In addition, we will highlight understudied areas with regard to microvascular protection afforded by antecedent ethanol in the hopes that this will stimulate investigation of its underlying mechanisms. Understanding these signaling pathways may provide a mechanistic rationale for the development of novel treatment interventions that target both the microcirculatory and parenchymal sequelae to I/R, thereby maximizing the therapeutic potential of the protected phenotypes produced by pharmacologic preconditioning.