[Coronary endothelial dysfunction after ischemia-reperfusion: mechanisms and possibilities for protection]

Although cardiac ischaemia-reperfusion is well known as a disease of the myocytes, it is now clear that its consequences also extend to the vascular wall and especially to the endothelial cells. Using a rat model of ischaemia-reperfusion in vivo, we evidenced an impairment of the NO-dependent relaxation to acetylcholine of coronary artery segments. Moreover, we showed that cultured endothelial cells submitted to anoxia/reoxygenation displayed an increased neutrophil adhesion, associated with an increased expression of adhesion molecules, probably responsible for the endothelial injury. In this context, we focused on the concept of endogenous protection against ischaemia, i.e. preconditioning, and demonstrated that endothelial dysfunction could be reversed by both the early and the delayed phase of preconditioning. The delayed endothelial preconditioning mechanism appears to involve complex interactions between NO and free radicals, leading to delayed improvement of NO production and decreased neutrophil adhesion to the endothelium. Identification of these mechanisms may lead to the development of new endothelial protective agents in pathophysiological situations associated with endothelial dysfunction.