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- Title
Arachidonic acid epoxygenase and 12( S)-lipoxygenase: evidence of their concerted involvement in ductus arteriosus constriction to oxygen.
- Authors
Baragatti, Barbara; Coceani, Flavio
- Abstract
Oxygen promotes closure of the ductus arteriosus at birth. We have previously presented a scheme for oxygen action with a cytochrome P450 (CYP450) hemoprotein and endothelin-1 (ET-1) being, respectively, sensor and effector, and a hypothetical monooxygenase product serving as a coupling link. We have also found in the vessel arachidonic acid (AA) 12( S)-lipoxygenase (12-lipoxygenase) undergoing upregulation at birth. Here, we examined the feasibility of a sensor-to-effector messenger originating from AA monooxygenase and 12-lipoxygenase pathways. The epoxygenase inhibitor, N-methylsulfonyl-6-(2-)hexanamide, suppressed the tonic contraction of ductus to oxygen. A similar effect was obtained with 12-lipoxygenase inhibitors baicalein and PD 146176. By contrast, none of the inhibitors modified the endothelin-1 contraction. Furthermore, an AA ω-hydroxylation product, 20-hydroxyeicosatetraenoic acid (20-HETE), reportedly responsible for oxygen contraction in the systemic microvasculature, had no such effect on the ductus. We conclude that AA epoxygenase and 12-lipoxygenase jointly produce a hitherto uncharacterized compound acting as oxygen messenger in the ductus.
- Subjects
ARACHIDONIC acid; LIPOXYGENASES; DUCTUS arteriosus abnormalities; STENOSIS; CYTOCHROME P-450; OXYGEN in the body; NEWBORN infant physiology
- Publication
Canadian Journal of Physiology & Pharmacology, 2011, Vol 89, Issue 5, p329
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y11-025