Role of lipoxygenase, cyclooxygenase and cytochrome P-450 metabolites in contractions of isolated guinea pig pulmonary venules induced by hypoxia and anoxia.
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.
Tracey
W R
WR
Department of Medicine, University of Western Ontario, London, Canada.
Bend
J R
JR
Hamilton
J T
JT
Paterson
N A
NA
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D015289:Leukotrienes / Q000494:pharmacology / Q000502:physiology*; D008084:Lipoxygenase / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000098:blood supply*; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D014680:Veins / Q000502:physiology*; D014699:Venules / Q000502:physiology*; D019324:beta-Naphthoflavone
D000098:Acetophenones; D001571:Benzoflavones; D002867:Chromones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011725:Pyridines; C013109:metapyrone; D000001:Calcimycin; D019324:beta-Naphthoflavone; C034338:FPL 57231; D009637:Masoprocol; D003577:Cytochrome P-450 Enzyme System; C049043:LY 163443; D011464:Epoprostenol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C035296:piriprost