Faculty Collaboration Database

Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 1999 Sep 30;401(6752):493-7

Date

10/16/1999

Pubmed ID

10519554

DOI

10.1038/46816

Scopus ID

2-s2.0-0033619262 (requires institutional sign-in at Scopus site)   827 Citations

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.

Author List

Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, Busse R

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Animals
Arachidonic Acid
Biological Factors
Bradykinin
Cells, Cultured
Coronary Vessels
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 2
Endothelium, Vascular
Enzyme Induction
Humans
In Vitro Techniques
Molecular Sequence Data
Oligonucleotides, Antisense
Oxygenases
Reverse Transcriptase Polymerase Chain Reaction
Swine
Vasodilation