Possible mechanisms of 15-hydroperoxyarachidonic acid-induced contraction of the canine basilar artery in vitro.

Pharmacological studies of the contraction induced by 15-hydroperoxyarachidonic acid (15-HPAA) were done in the isolated canine basilar artery. The maximal contractile force produced by 15-HPAA was 1.5 times that of serotonin and was equivalent to that of prostaglandin (PG) F2 alpha or PGA1. At concentrations in which reductions of [14C]-6-keto-PGF1 alpha (the breakdown product of PGI2) occurred, both 15-HPAA and tranylcypromine contracted the artery, whereas indomethacin consistently relaxed it. In the case of indomethacin, as the drug inhibited the synthesis of [14C]-PGE2, F2 alpha and thromboxane(TX) B2 (the breakdown product of TXA2) as well, it has been considered that the balances between PGI2 and other vasoconstrictive PGs or TX may regulate the tone of the artery. Furthermore, it was shown that 15-HPAA enhanced the synthesis of lipoxygenase products from [14C]arachidonic acid. Experiments were done, therefore, to know whether these enhanced lipoxygenase products participated in the manifestation of contraction induced by 15-HPAA or not. As a result, although indomethacin did not affect the contraction, significant reductions of the contraction were shown by eicosatetraynoic acid. These results suggest that enhanced synthesis of lipoxygenase products may be involved in eliciting contractile responses of 15-HPAA.