Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 1999 Sep 30;401(6752):493-7
Date
10/16/1999Pubmed ID
10519554DOI
10.1038/46816Scopus ID
2-s2.0-0033619262 (requires institutional sign-in at Scopus site) 832 CitationsAbstract
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 RAuthor
David Harder PhD, MS Emeritus Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
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
