RELAXATIONS INDUCED BY LIPOXYGENASE METABOLITES OF ARACHI-DONIC ACID IN SPLENIC ARTERIES OF THE DOG

Abstract

The lipoxygenase metabolites of arachidonic acid, 15 hydroperoxyeicosatetraenoic acid (15HPETE) and its hydroxy derivative (15HETE) evoke contractions in a variety of isolated blood vessels. We recently were able to show that thromboxane A2 (TXA2)-receptor antagonists BM13177 and BM13505 suppress the contractions induced by lipoxygenase metabolites in canine splenic arteries, and that these compounds also inhibit the contractile effects of PGF2α and of the TXA2-mimetic U46619. We also reported that 15HETE and 15HPETE cause relaxations of isolated dog arteries when the tissues are contracted with prostaglandin F2α (PGF2α) or with U46619 and suggested that lipoxygenase metabolites may act as endogenous antagonists towards prostaglandin receptors. The present study was designed to investigate the effects of lipoxygenase metabolites of arachidonic acid in isolated splenic arteries in which the tone is raised by various agonists.Segments of canine splenic arteries with or without endothelium were placed in organ chambers filled with Krebs-Ringer solution at 37°C for isometric tension recording. Responses to 15HPETE were obtained in segments which were contracted with serotonin, K+, PGF2α or noradrenaline (the latter with or without BM13505); concentrations causing comparable levels of contraction were selected. HPETE evoked relaxations in segments with and without endothelium, during the contractions evoked by K+, PGF2α and noradrenaline (with or without BM13505). At higher concentrations, 15HPETE caused relaxations only during contractions induced by PGF2α and noradrenaline with BM13505. Our results suggest that 15HPETE can cause relaxations by two different mechanisms :(1) 15HPETE may act as an antagonist to PGF2α, which causes its contraction via the TXA2-receptor and,(2) in presence of BM13505, it suppresses the contractions to noradrenaline via an endothelium independent mechanism.