© 2007 European Society of Cardiology
Cytochrome P450 2C9 is involved in flow-dependent vasodilation of peripheral conduit arteries in healthy subjects and in patients with chronic heart failure
a Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover Hannover, Germany
b Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann-Wolfgang-Goethe-Universität Frankfurt am Main Germany
* Corresponding author. Medizinische Hochschule Hannover, Abteilung Kardiologie und Angiologie, Carl Neuberg Str. 1, 30625 Hannover, Germany. Tel.: +49 511 532 3840; fax: +49 511 532 5412 E-mail address: Drexler.Helmut{at}MH-Hannover.DE.
 |
Abstract |
|---|
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.
Key Words: EDHF • Chronic heart failure • Endothelial function
Received November 9, 2006; Revised March 11, 2007; Accepted May 3, 2007
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Krotz, N. Hellwig, M. A. Burkle, S. Lehrer, T. Riexinger, H. Mannell, H.-Y. Sohn, V. Klauss, and U. Pohl A sulfaphenazole-sensitive EDHF opposes platelet-endothelium interactions in vitro and in the hamster microcirculation in vivo Cardiovasc Res, October 4, 2009; (2009) cvp301v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rudolph and B. A. Freeman Cardiovascular Consequences When Nitric Oxide and Lipid Signaling Converge Circ. Res., September 11, 2009; 105(6): 511 - 522. [Abstract] [Full Text] [PDF]
|
|