Cytochrome P450 2C expression and EDHF-mediated relaxation in porcine coronary arteries is increased by cortisol.
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Bauersachs J, Christ M, Ertl G, Michaelis UR, Fisslthaler B, Busse R, Fleming I
Cytochrome P450 2C expression and EDHF-mediated relaxation in porcine coronary arteries is increased by cortisol.
Cardiovasc Res. 2002 Jun;54(3):669-75.
- PubMed ID
- 12031713 [ View in PubMed]
- Abstract
OBJECTIVES/METHODS: In addition to nitric oxide (NO) and prostacyclin, endothelium-dependent dilation is mediated by the endothelium-derived hyperpolarizing factor (EDHF) which, in the coronary circulation, has been characterised as a metabolite of arachidonic acid synthesised by an cytochrome P450 (CYP) epoxygenase homologous to CYP 2C8/9. As the promotor regions of CYP 2C8 and 2C9 contain consensus sequences for glucocorticoid response elements, we determined the effect of cortisol on EDHF-mediated relaxations as well as on the expression of CYP 2C in isolated segments of porcine coronary artery. RESULTS: Bradykinin-induced NO-mediated relaxation of KCl-constricted arterial rings was slightly attenuated following exposure to cortisol. However, EDHF-mediated relaxations of U46619-constricted arterial rings assessed in the presence of the cyclo-oxygenase inhibitor diclofenac and the NO synthase inhibitor N(omega)nitro-L-arginine (0.3 mM), were significantly enhanced (maximum relaxation: 66+/-7%, P<0.05 vs. control rings: 36+/-8%). Cortisol treatment (0.1 microM, 24 h) did not affect the endothelium-independent relaxation elicited by sodium nitroprusside and acute incubation with cortisol (0.1 microM, 30 min) did not alter either NO- or EDHF-mediated responses. The expression of CYP 2C (quantified by RT-PCR, Western blot analysis and confocal microscopy) was enhanced in porcine coronary endothelial cells following incubation with cortisol for 18-24 h. CONCLUSIONS: These results demonstrate the concomitant upregulation of EDHF-mediated relaxations and CYP 2C expression by long-term treatment with cortisol. These observations support the concept that an epoxygenase homologous to CYP 2C8/9 plays a crucial role in the generation of EDHF-mediated responses in the coronary endothelium.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Hydrocortisone Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone aceponate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone acetate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone butyrate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone cypionate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone phosphate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone probutate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone succinate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails Hydrocortisone valerate Cytochrome P450 2C8 Protein Humans UnknownInducerDetails