Cyclo-oxygenase blockers influence the effects of 15-lipoxygenase metabolites of arachidonic acid in isolated canine blood vessels

Abstract

In canine saphenous veins both the 15-hydroxy- and 15-hydroperoxy derivatives of arachidonic acid, 15HETE and 15HPETE, caused endothelium-independent contractions which were not affected by a variety of classical receptor antagonists. These contractions were markedly augmented by cyclooxygenase blockers; nifedipine, which did not influence the contractions induced by lipoxygenase products, inhibited the potentiating effect of indomethacin. In the veins, 15HETE and 15HPETE also induced spontaneous rhythmic contractions which persisted after several washings but could be blocked by inhibitors of cyclooxygenase. In coronary, splenic, renal and femoral arteries, 15HETE and 15HPETE caused contractions which were also augmented by indomethacin and were dependent on the influx of extracellular calcium as they were inhibited by verapamil. Both 15-lipoxygenase metabolites evoked relaxations during contractions induced by prostaglandin F2 alpha or the thromboxane-mimetic U46619. These relaxations were not endothelium-dependent but were inhibited by indomethacin; they did not occur when the initial contractions were caused by K+, norepinephrine or 5-HT. Our results illustrate multiple vascular actions of 15HETE and 15HPETE in dog blood vessels.