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endothelium to severe structural alterations of the
vasculature, and finally to vascular thrombosis and the no-
reflow phenomenon, which may underly reperfusion
injury. The endothelium plays a relevant role in the
regulation of the coronary circulation, and it could exist a
functional interaction between NO and ET-1 in the
coronary artery wall, with predominance of NO over ET-1
and also with a relevant role of NO in modulation of
coronary effects of ET-1under normal conditions. The
endothelium seems to be highly sensitive to ischemia, and
after ischemia-reperfusion the endothelial function and the
interaction between NO and ET-1are altered, and now ET-
1 predominates over NO and the modulator role of NO in
the effects of ET-1 is decreased. These features lead to
decreased endothelium-dependent coronary vasodilatation,
particularly that mediated by NO, and also to increased
coronary vasoconstrictor response to ET-1. After
ischemia-reperfusion, the production of ET-1 seems to be
augmented, and the equilibrium between endothelin
receptors may be altered with an increased role of the
smooth muscle cells ETA and ETB receptors in the
augmented coronary vasoconstriction to ET-1. It is
probable that ischemia-reperfusion by damaging the
endothelium it decreases the NO-mediated vasodilation of
coronary vessels, and at the same time it augments the
production of ET-1 and its coronary vasoconstrictors
effects. This damage of the endothelium and the
augmented presence of ET-1 and of its coronary effects,
would contribute to produce vascular dysfunction, vascular
damage, vascular thrombosis and the non-reflow
phenomenon, thus contributing to reperfusion injury. From
these considerations, it can be suggested that ET-1 plays a
significant role in pathophysiology of coronary ischemia-
reperfusion and of reperfusion injury, and therefore it is
reasonable to expect that the use of antagonists for
endothelin ETA and ETB receptors could be beneficial for
protecting the heart against this condition.
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