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Coronary ischemia-reperfusion: role of nitric oxide and endothelin-1. A Review

from patients suggest that high plasma ET-1 levels after of spontaneous reperfusion, and the ET-1 level at
myocardial infarction are associated with the presence of admission is an indicator of spontaneous reperfusion (173).
microvascular obstruction and lower myocardial salvage L. Cao et al. (174), after considering observations by
index (171). others, suggest that ET-1 may act as a negative factor in
reperfusion injury. These authors also suggest that ET-1
An interesting study was performed in patients with plays a different role in the different stages of myocardial
AMI that underwent reperfusion therapy or conservative ischemia-reperfusion, and to ascertain the exact
drug therapy. Patients who underwent reperfusion therapy mechanisms, experimental and clinical studies are needed
had significantly lower eNOS and NO levels, and higher (174). On the other hand, it can not be excluded that after
plasma ET-1 levels than those who received conservative ischemia-reperfusion, ET-1 also may induce beneficial
drug therapy. All patient groups had significantly lower effects on the myocardium. ET-1 could induce
eNOS and NO levels, and higher ET-1 levels, than healthy cardioprotection against infarct size and ventricular
controls. There was a significant positive correlation arrhythmias, through as yet incompletely understood
between eNOS and NO, as well as significant negative mechanisms (175), as well subsequent infarct-healing and
correlations between eNOS/ET-1 and NO/ET-1 (172). In early ventricular remodeling (166, 176).
other study it has been found that the circulating level of
ET-1 was considerably higher in the non-spontaneous Data from literature suggest that ET-1 plays a relevant
reperfusion patients than in the spontaneous reperfusion role in development of coronary artery disease and in the
patients; the ET-1 level was the only significant predictor effects of myocardial ischemia-reperfusion (Figure 11).

Figure 11. Schematic representation of the probable role of ET-1 in the pathophysiology of coronary artery disease, myocardial
infarction, and heart failure. At preclinical stages, ET-1 could contribute to endothelial cell dysfunction and to atherosclerosis. During
acute coronary syndromes, ET-1 could cause adverse effects (vasoconstriction, inflammation, myocardial necrosis, arrhythmogenesis),
and during chronic evolution it might have beneficial effects by participating in infarct healing.

The study of the effects of ET-1 and its interaction with diminish the adverse effects of ischemia-reperfusion (178).
NO in coronary vasculature after ischemia-reperfusion Other studies, however, showed that inhibitions of NO
may contribute to know its pathophysiology. Respect to synthesis may protect, rather than aggravate, the effects of
this issue, most of studies have been related with the ischemia-reperfusion (18, 179). For ET-1, ischemia-
analysis of the effects of total ischemia followed by reperfusion can induce increased coronary
reperfusion, and very few studies have been performed vasoconstriction in response to this peptide (180) but
about the effects of partial ischemia alone or followed by whether or not this increased effect is present may depend
reperfusion. The clinical situation of partial ischemia of on the severity and duration of ischemia (181). The
the myocardium may be present in patients with coronary increased response to ET-1 after ischemia-reperfusion it
atheromatosis, dynamic vasospasm, or transient arterial has been attributed to decreased production of NO and
hypotension. prostacyclin as a result of endothelial dysfunction, and of
changes in characteristics of endothelin receptors in
During reperfusion after total (134) or partial (140) coronary vessels (180, 182). The coronary reactivity to
coronary occlusion, endothelium-dependent coronary ET-1 after ischemia-reperfusion has been explored mainly
vasodilatation is decreased. Also, basal release of NO from using in vivo and in vitro preparations, and coronary
isolated, perfused rat hearts may be diminished after global ischemia for different periods has been induced in vivo by
ischemia-reperfusion, with implication of the NO pathway occluding one coronary artery and in isolated, perfused
(177). On the hand, administrations of exogenous NO hearts.

@Real Academia Nacional de Farmacia. Spain 31