Cytochrome P450 2C is an EDHF synthase in coronary arteries

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Item Type:	Article
Title:	Cytochrome P450 2C is an EDHF synthase in coronary arteries
Creators Name:	Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I. and Busse, R.
Abstract:	In most arterial beds a significant endothelium-dependent dilation to various stimuli persists even after inhibition of nitric oxide synthase and cyclo-oxygenase. This dilator response is preceded by an endothelium-dependent hyperpolarization of vascular smooth muscle cells, which is sensitive to a combination of the calcium-dependent potassium-channel inhibitors charybdotoxin and apamin, and is assumed to be mediated by an unidentified endothelium-derived hyperpolarizing factor (EDHF). Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of EDHF-mediated relaxation in the porcine coronary artery, and CYP 2C8/34 fulfils the criteria for the coronary EDHF synthase.
Keywords:	8,11,14-Eicosatrienoic Acid, Antisense Oligonucleotides, Arachidonic Acid, Biological Factors, Bradykinin, Coronary Vessels, Cultured Cells, Cytochrome P-450 Enzyme System, Cytochrome P450 Family 2, Enzyme Induction, In Vitro Techniques, Molecular Sequence Data, Oxygenases, Reverse Transcriptase Polymerase Chain Reaction, Vascular Endothelium, Vasodilation, Animals, Swine
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	401
Number:	6752
Page Range:	493-497
Date:	30 September 1999
Official Publication:	https://doi.org/10.1038/46816
PubMed:	View item in PubMed

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