Role of lipoxygenase and cytochrome P-450 in production of endothelium- derived relaxing factors in canine femoral veins

D. A. Lewis, Virginia M Miller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10-5 M) or TMK777 (10-6 M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10-6 M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10-6 M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10-5 M) and N(G)-monomethyl-L-arginine (L-NMMA 10-4 M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F(2α). AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide.

Original languageEnglish (US)
Pages (from-to)401-407
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume20
Issue number3
StatePublished - 1992

Fingerprint

omega-N-Methylarginine
Endothelium-Dependent Relaxing Factors
Femoral Vein
Lipoxygenase
Arachidonate Lipoxygenases
Indomethacin
Cytochrome P-450 Enzyme System
Proadifen
Endothelium
Canidae
Lipoxygenase Inhibitors
Thrombin
Veins
Nitric Oxide
Masoprocol
Thrombin Receptors
Calcimycin
Prostaglandins F
Prostaglandin-Endoperoxide Synthases
Adenosine Diphosphate

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Endothelium-derived relaxing factors
  • Lipoxygenase
  • Veins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

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title = "Role of lipoxygenase and cytochrome P-450 in production of endothelium- derived relaxing factors in canine femoral veins",
abstract = "We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10-5 M) or TMK777 (10-6 M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10-6 M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10-6 M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10-5 M) and N(G)-monomethyl-L-arginine (L-NMMA 10-4 M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F(2α). AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide.",
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AB - We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10-5 M) or TMK777 (10-6 M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10-6 M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10-6 M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10-5 M) and N(G)-monomethyl-L-arginine (L-NMMA 10-4 M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F(2α). AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide.

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