Helmholtz Gemeinschaft


Cytochrome P450 2C is an EDHF synthase in coronary arteries

Item Type:Article
Title:Cytochrome P450 2C is an EDHF synthase in coronary arteries
Creators Name:Fisslthaler, B. and Popp, R. and Kiss, L. and Potente, M. and Harder, D.R. and 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
Publisher:Nature Publishing Group
Page Range:493-497
Date:30 September 1999
Official Publication:https://doi.org/10.1038/46816
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library