Epoxyeicosatrienoic Acid And Endothelium-Dependent Hyperpolarization In Porcine Coronary Arteries

11, 12-epoxyeicosatrienoic acid was proposed to be the hyperpolarizing factor in porcine coronary arteries (Fisslthaler et al., 1999). To test this hypothesis, the pharmacology of the hyperpolarizing effects of 11,12-epoxyeicosatrienoic acid and the endothelium-derived hyperpolarizing factor (elicited with substance P) in the porcine coronary artery were compared using sharp micro-electrode techniques. The hyperpolarizations of smooth muscle induced either by substance P or by 11,12-epoxyeicosatrienoic acid in intact porcine coronary arteries were abolished by charybdotoxin plus apamin but only moderately inhibited by iberiotoxin plus apamin. However, in coronary arteries without endothelium the hyperpolarization induced by 11,12-epoxyeicosatrienoic acid was abolished by iberiotoxin alone. In intact arteries, 11,12-epoxyeicosatrienoic acid induced an iberiotoxin-insensitive hyperpolarization of the endothelial cells. These results collectively suggest that 11,12-epoxyeicosatrienoic acid is not an endothelium-derived hyperpolarizing factor in the porcine coronary artery. Instead it seems that this eicosanoid has two basic effects. One of these is to hyperpolarize coronary artery smooth muscle directly via the opening of an iberiotoxin-sensitive potassium channel (presumably BKCa) in these cells. The other is hyperpolarization of the endothelium, an action involving the opening of both apamin- and charybdotoxin(but not iberiotoxin-) sensitive potassium channels (presumably SKCa, and IKCa, respectively).