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Arachidonic Acid Epoxygenase and 12(S)-lipoxygenase: Evidence of Their Concerted Involvement in Ductus Arteriosus Constriction to Oxygen

Arachidonic Acid Epoxygenase and 12(S)-lipoxygenase: Evidence of Their Concerted Involvement in Ductus Arteriosus Constriction to Oxygen

Barbara Baragatti, Flavio Coceani

Can J Physiol Pharmacol. 2011 May;89(5):329-34.

PMID: 21619415

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP4079269	PD 146176		4079-26-9	Price

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