chapter  24
8 Pages

Lipoxygenase-derived metabolites of arachidonic acid are not involved in the endothelium-dependent hyperpolarization to acetylcholine in the carotid artery of the guinea-pig

The present study was designed to determine whether or not lipoxygenase-dependent metabolites of arachidonic acid are involved in the endothelium-dependent hyperpo­ larization of the carotid artery of the guinea-pig. The specific 12-lipoxygenase inhibitor cinnamyl-3,4 dihydroxy-a-cyanocinnamate (CDC) , the non-specific inhibitor of lipoxy­ genase, cycloxygenase and cytochrome P450 eicosatetraynoic acid ( E T Y A ) , and the inhibitors of phospholipase A 2 A A C O C F 3 and quinacrine did not significantly affect the membrane potential of the vascular smooth muscle cells while the 5-lipoxygenase inhibitor AA861 produced a significant hyperpolarization. Acetylcholine-induced hyperpolarizations were not significantly affected by A A C O C F 3 , E T Y A and quina­ crine. In contrast, C D C at l f r 5 M (but not at ÎO" 6 M ) and AA861 ( l f r 6 and 10" 5 M ) produced a partial but significant inhibition of the hyperpolarization. (±)12-Hydroxyeicosatetraenoic acid (12-HETE, 10~ 6 M) and 12(S)-hydroperoxy-eicosatetraenoic acid (12(S)-HpETE, 3 x l f r 6 M ) did not induce significant changes in membrane potential. In isolated vascular smooth muscle cells, C D C inhibited voltage-gated potassium cur­ rents sensitive to 4-aminopyridine and increased calcium-activated potassium currents sensitive to charybdotoxin while AA861 inhibited both potassium currents. These results suggest that lipoxygenase-dependent metabolites of arachidonic acid are unlikely to be involved in the acetylcholine-induced endothelium-dependent hyperpolarization of the carotid artery of the guinea-pig.