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Cytochrome P450 2C9 is involved in flow‐dependent vasodilation of peripheral conduit arteries in healthy subjects and in patients with chronic heart failure
Author(s) -
Fischer Dieter,
Landmesser Ulf,
Spiekermann Stephan,
HilfikerKleiner Denise,
Hospely Marian,
Müller Maja,
Busse Rudi,
Fleming Ingrid,
Drexler Helmut
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.05.005
Subject(s) - medicine , vasodilation , cardiology , heart failure , endothelial dysfunction , artery , endothelium , anesthesia
Background Flow‐mediated dilation (FMD) of human conduit arteries is, in part, related to shear stress‐induced release of endothelium‐derived nitric oxide (NO). However, NO synthase inhibitors do not completely abolish this FMD‐response. Recently, a cytochrome P450 (CYP) epoxygenase of the 2C family was linked to NO‐ and prostacyclin‐independent relaxation of conduit arteries. We therefore evaluated the contribution of CYP 2C9 to FMD in humans. Methods and results FMD of the radial artery was determined in 12 healthy volunteers by high‐resolution ultrasound and analyzed before and after intra‐arterial infusion of sulfaphenazole, a specific CYP 2C9 inhibitor, L ‐NMMA (NO synthase inhibitor) and co‐infusion of both. Endothelium‐independent vasodilation was characterized after intra‐arterial infusion of SNP. FMD was reduced after sulfaphenazole (11.5±0.87% vs . 7.4±0.95%, p <0.01), after L ‐NMMA (6.0±0.71%; p <0.01), and after co‐infusion 3.9±0.73% ( p <0.05 vs . L ‐NMMA; p <0.01 vs . sulfaphenazole). Sulfaphenazole had no effect on endothelium‐independent vasodilation. In patients with chronic heart failure, the portion of FMD blocked by sulfaphenazole was not affected. CYP 2C was detected by immunohistochemistry in radial artery samples obtained from patients undergoing coronary bypass surgery. Conclusions FMD in human conductance arteries is reduced after inhibition of CYP 2C9, supporting the concept that CYP 2C metabolites contribute to endothelium‐mediated vasodilation of peripheral conduit arteries in vivo . In patients with heart failure, the CYP‐dependent FMD appears to be preserved.