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This Article Full Text Full Text (PDF) All Versions of this Article: 289/3/H1077    most recent 01046.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by You, J. Articles by Bryan, R. M. Search for Related Content PubMed PubMed Citation Articles by You, J. Articles by Bryan, R. M., Jr.

Arachidonic acid metabolites, hydrogen peroxide, and EDHF in cerebral arteries

¹Cerebrovascular Research Laboratory, Department of Anesthesiology, and ²Division of Cardiovascular Sciences, Department of Medicine and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas

Submitted 10 October 2004 ; accepted in final form 21 April 2005

We tested the hypotheses that EDHF in rat middle cerebral arteries (MCAs) involves 1) metabolism of arachidonic acid through the epoxygenase pathway, 2) metabolism of arachidonic acid through the lipoxygenase pathway, or 3) reactive oxygen species. EDHF-mediated dilations were elicited in isolated and pressurized rat MCAs by activation of endothelial P2Y₂ receptors with either UTP or ATP. All studies were conducted after the inhibition of nitric oxide synthase and cyclooxygenase with N-nitro-L-arginine methyl ester (10 µM) and indomethacin (10 µM), respectively. The inhibition of epoxygenase with miconazole (30 µM) did not alter EDHF dilations to UTP, whereas the structurally different epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanoic acid (20 or 40 µM) only modestly inhibited EDHF at the highest concentration of UTP. An antagonist of epoxyeicosatrienoic acids, 14,15-epoxyeicosa-5(Z)-enoic acid, had no effect on EDHF dilations to UTP. Chronic inhibition of epoxygenase in the rat with 1-aminobenzotriazol (50 mg/kg twice daily for 5 days) did not alter EDHF dilations. The inhibition of the lipoxygenase pathway with either 10 µM baicalein or 10 µM nordihydroguaiaretic acid produced no major inhibitory effects on EDHF dilations. The combination of superoxide dismutase (200 U/ml) and catalase (140 U/ml) had no effect on EDHF dilations. Neither tiron (10 mM), a cell-permeable scavenger of reactive oxygen species, nor deferoxamine (1 or 10 mM), an iron chelator that blocks the formation of hydroxyl radicals, altered EDHF dilations in rat MCAs. We conclude that EDHF dilations in the rat MCA do not involve the epoxygenase pathway, lipoxygenase pathway, or reactive oxygen species including H₂O₂.

adenosine triphosphate; endothelium; endothelium-derived hyperpolarizing factor; epoxyeicosatrienoic acids; epoxygenase; hydroxyl radical; lipoxygenase; reactive oxygen species; superoxide anion; uridine triphosphate

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