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

Figure 5. Actual recordings of the coronary effects of ET-1obtained in one anesthetized goat (left) and in one isolated, perfused rat heart
(right); I. c. =intracoronary.

There are studies suggesting that the coronary by IRL 1620 were not changed. Meclofenamate
vasoconstriction by ET-1 is mediated by ETA receptors (cyclooxygenase inhibitor) modified neither the basal
in humans (91), pigs (92) and rats (93), and that the role values of hemodynamic variables nor the coronary
of ETB receptors is not clear, although it may be of less effects of ET-1 and IRL 1620. Therefore, ET-1 produces
significance (91). Balwierczak (94) reports data pronounced coronary vasoconstriction, which may be
suggesting that coronary response to ET-1 is mediated by mediated by endothelin ETA receptors, with no
both ETA and ETB receptors. With regard to the role of participation of endothelin ETB receptors; NO, but not
NO, it has been suggested that ET-1 can release NO in prostanoids, may inhibit ET-1-induced coronary
the coronary vasculature, and that this NO induces vasoconstriction. Also, it is suggested that the coronary
vasodilatation (92, 95) and counteracts the vasoconstriction by ET-1 may impair cardiac
vasoconstriction produced by ET-1 (93). Regard to the performance due to heart ischemia (96). From the studies
role of prostanoids, the results reported are contradictory with ET-1 and L-NAME in isolated, perfused hearts from
(93, 95). In our laboratory, we observed that ET-1, rats (89) and in isolated coronary arteries from pigs (90)
intracoronarily injected, produced marked reductions in similar conclusions can be obtained about the modulatory
coronary blood flow, and that these effects were role of NO in the coronary effects of ET-1 (see below
diminished by BQ-123, specific antagonist for endothelin Ischemia-reperfusion). Figure 6 shows an estimation of
ETA receptors, but not during the infusion of BQ-788, possible interaction between NO and ET-1 in the
specific antagonist for endothelin ETB receptors. IRL coronary circulation derived from the observed effects of
1620, specific agonist for endothelin ETB receptors, inhibition of NO synthesis with L-NAME on the
intracoronarily injected, slightly reduced basal coronary coronary response to ET-1 in anesthetized goats (96),
blood flow. The effects of IRL 1620 were not modified isolated hearts from rats (89) and isolated coronary
by BQ-123 or BQ-788. With L-NAME, the reductions of arteries from pigs (90).
coronary blood flow by ET-1 were potentiated and those

Figure 6. Summary of the effects of inhibition of NO synthesis with L-NAME on the action of ET-1 in the coronary circulation of
anesthetized goats (A) and of isolated, perfused hearts from rats (B), as well as in isolated coronary arteries from pigs (C). The
augmentation of the coronary response to ET-1 was qualitatively similar in the three experimental preparations.

@Real Academia Nacional de Farmacia. Spain 23