Evidence against a role for lipoxygenase-derived products of arachidonic acid in the lamb ductus arteriosus

Publisher Website
Google Scholar
Abstract
The effects of leukotrienes, the leukotriene antagonist FPL55712 (sodium 7-(3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate), and inhibitors of arachidonate lipoxygenase and cyclooxygenase (compound BW755C, 3-amino-1-(m-(trifluoromethyl)-phenyl)-2-pyrazoline; ETYA, 5,8,11,14-eicosatetraynoic acid) were studied in an isolated preparation of ductus arteriosus from mature fetal lambs. Leukotrienes (LT) C4 and D4 produced a modest relaxation of the ductus, but only at the highest concentrations tested (10-7-10-6 M) and under hypoxic conditions (PO2 [O2 partial pressure], 6-9 torr (1 torr = 133.322 Pa [pascal])). LTB4 had no effect at any concentration tested. BW755C (10-6-10-5 M) and FPL55712 (10-5 M) contracted the hypoxic ductus; their action was abolished by pretreatment of the tissue with the cyclooxygenase inhibitor indomethacin (2.8 .times. 10-6 M). Indomethacin-treated preparations were also unresponsive to ETYA 3 .times. 10-5 M. The contraction of hypoxic tissues to BW755C or FPL55712 increased further upon raising the PO2 of the medium (PO2 591 to 691 torr). Leukotrienes and allied compounds formed from lipoxygenase-catalyzed reactions do not contribute to prenatal patency of the ductus and are unlikely to have a role in its closure at birth. Prostaglandin E2 is essential for keeping the vessel patent in the fetus.

This publication has 1 reference indexed in Scilit: