Role of lipoxygenase, cyclooxygenase and cytochrome P-450 metabolites in contractions of isolated guinea pig pulmonary venules induced by hypoxia and anoxia.

Abstract

Arachidonic acid metabolites, notably leukotrienes (LTs), have been postulated to play a role in hypoxic pulmonary vasoconstriction. In the present study, we examined the contribution of arachidonic acid metabolites, via the cyclooxygenase, 5-lipoxygenase and cytochrome P-450 monooxygenase pathways, to the hypoxia (25 +/- 3 torr)- and anoxia (0 +/- 2 torr)-induced contractions of isolated pulmonary venules. Neither the cyclooxygenase inhibitors indomethacin (5 microM) or ibuprofen (10 microM) nor the 5-lipoxygenase inhibitors nordihydroguaiaretic acid (5 microM) or U 60257B (10 microM) affected the contractile responses. Similarly, the LT receptor antagonists FPL 57231 (3 microM) or LY 163443 (1 microM), at concentrations that inhibited LT-induced venular contractions, did not significantly affect the responses to hypoxia or anoxia. In fact, anoxia suppressed spontaneous LT release from the venules. The cytochrome P-450 inhibitor SKF-525A (500 microM) nonselectively depressed venular contractions induced by decreased PO2 and pharmacological agents. Induction of the cytochrome P-450 monooxygenase system with beta-naphthoflavone did not alter venular contractions induced by hypoxia or anoxia. Contractions of isolated guinea pig pulmonary venules elicited by decreased PO2 are not mediated by 5-lipoxygenase or cyclooxygenase metabolites. Furthermore, the data do not support a role for cytochrome P-450 metabolites of endogenous substrates in these contractions.

• Authors: W R Tracey, J R Bend, J T Hamilton, N A Paterson
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 250 Issue 3 Pg. 1097-104 (Sep 1989) ISSN: 0022-3565 [Print] United States
• PMID: 2506335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Benzoflavones
• Chromones
• Leukotrienes
• Lipoxygenase Inhibitors
• Pyridines
• metapyrone
• Calcimycin
• beta-Naphthoflavone
• FPL 57231
• Masoprocol
• Cytochrome P-450 Enzyme System
• LY 163443
• Epoprostenol
• Lipoxygenase
• Prostaglandin-Endoperoxide Synthases
• piriprost

Topics

• Acetophenones (pharmacology)
• Animals
• Benzoflavones (pharmacology)
• Calcimycin (pharmacology)
• Chromones (pharmacology)
• Cytochrome P-450 Enzyme System (physiology)
• Epoprostenol (pharmacology)
• Guinea Pigs
• Hypoxia (physiopathology)
• Leukotrienes (pharmacology, physiology)
• Lipoxygenase (physiology)
• Lipoxygenase Inhibitors
• Lung (blood supply)
• Masoprocol (pharmacology)
• Muscle Contraction (drug effects)
• Muscles
• Prostaglandin-Endoperoxide Synthases (physiology)
• Pyridines (pharmacology)
• Veins (physiology)
• Venules (physiology)
• beta-Naphthoflavone