title: EDHF: a cytochrome P450 metabolite in coronary arteries.
abstract: Endothelium-dependent relaxation cannot be fully attributed to the release of nitric oxide or prostacyclin (PGI2). In resistance-sized vessels and coronary arteries a high proportion of endothelium-dependent relaxation, in response to agonist-induced or mechanical stimulation of endothelial cells, can be attributed to the release of 1 or more endothelium-derived hyperpolarizing factor (EDHF). In coronary arteries EDHF has been pharmacologically characterized as a cytochrome P450 (CYP)-derived metabolite of arachidonic acid. We show here that a CYP 2C arachidonic acid epoxygenase, homologous to CYP 2C8/9, is expressed in cultured human endothelial cells and native porcine coronary artery endothelial cells. Down-regulation of CYP 2C protein by transfection of porcine coronary arteries with anti-sense oligonucleotides decreased EDHF-mediated vascular responses while EDHF-mediated hyperpolarisation and relaxation were potentiated by the CYP-inducing compound beta-naphthoflavone. Thus, CYP 2C appears to play a crucial role in the generation of EDHF-mediated responses in porcine coronary arteries.
authors.affiliation: Institut für Kardiovaskuläre Physiologie Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany. Fisslthaler@em.uni-frankfurt.de
authors.forename: B
authors.initials: B
authors.lastname: Fisslthaler
authors.forename: I
authors.initials: I
authors.lastname: Fleming
authors.forename: R
authors.initials: R
authors.lastname: Busse
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D003331:Coronary Vessels / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D003577:Cytochrome P-450 Enzyme System