Endothelin-1 potentiation of coronary artery contraction after ischemia-reperfusion

Abstract Hearts from Sprague–Dawley rats were perfused at constant flow and then exposed to 30 min global zero-flow ischemia followed by 15 min reperfusion. After ischemia–reperfusion, coronary arteries were dissected from the heart and segments 2 mm long were prepared for isometric tension recording in organ baths. Stimulation of the arteries with 5-hydroxytryptamine (10 − 6  M) produced contraction, which was potentiated by treatment with endothelin-1 (3 × 10 − 10 ; 10 − 9  M). This potentiation was lower in the arteries from hearts after ischemia–reperfusion (for 3 × 10 − 10  M, 15 ± 5%; P  > 0.05; for 10 − 9  M, 37 ± 7%, P n  = 5) than after control (for 3 × 10 − 10  M, 34 ± 4%; P − 9  M, 50 ± 6%, P n  = 5), and the potentiation was reduced by the inhibitor of nitric oxide synthesis l -NAME (10 − 4  M), the antagonist of endothelin ET A receptors BQ123 (10 − 6  M) and the antagonist of endothelin ET B receptors BQ788 (10 − 6  M), but not by the cyclooxygenase inhibitor meclofenamate (10 − 5  M). These results suggest that endothelin-1 at low concentrations potentiates coronary vasoconstriction, and this effect is reduced after ischemia–reperfusion, mediated by endothelin ET A and ET B receptors and dependent on nitric oxide release.