The effects of the duration of
ischemia on coronary vasoconstriction after
ischemia-reperfusion were analysed in rat hearts. After 15, 30 or 45 min of global zero-flow
ischemia and 15 min reperfusion, the coronary response to
endothelin-1 (10(-10)-10(-7) M) and the
thromboxane A2 analogue 9,11-dideoxy-1a,9a-epoxymethanoprostaglandin F2alpha (U46691, 10(-8)-10(-6) M) was recorded. Vasoconstriction induced by
endothelin-1 only increased after short 15 min periods of
ischemia. In contrast, the vasoconstriction induced by
U46619 remained unmodified by short
ischemias but was reduced after longer periods of
ischemia (30 and 45 min). Inhibition of
nitric oxide synthesis with the Nw-nitro-
L-arginine methyl ester (L-NAME, 10(-4) M) augmented the vasoconstriction induced by
endothelin-1 in non-ischemic hearts, but not following
ischemia. Similarly,
L-NAME increased the vasoconstriction induced by
U46619 to a greater extent in non-ischemic hearts than following
ischemia. These results suggest that
ischemia-reperfusion inhibits
nitric oxide production, causing an increased coronary response to
endothelin-1 after brief
ischemias. Longer
ischemias may non-specifically inhibit coronary vasoconstriction and reduce
nitric oxide production.