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

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 x 10(-10); 10(-9) M). This potentiation was lower in the arteries from hearts after ischemia-reperfusion (for 3 x 10(-10) M, 15 +/- 5%; P>0.05; for 10(-9) M, 37 +/- 7%, P<0.01, n=5) than after control (for 3 x 10(-10) M, 34 +/- 4%; P<0.01; for 10(-9) M, 50 +/- 6%, P<0.01, n = 5), and the potentiation was reduced by the inhibitor of nitric oxide synthesis L-NAME (10(-4) M), the antagonist of endothelin ETA receptors BQ123 (10(-6) M) and the antagonist of endothelin ETB 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 ETA and ETB receptors and dependent on nitric oxide release. (C) 2008 Elsevier Inc. All rights reserved.