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(Circulation Research. 2006;98:866.)
© 2006 American Heart Association, Inc.

Editorials

Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus

David R. Harder, Richard J. Roman

From the Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee.

Correspondence to David R. Harder, Director, Cardiovascular Research Center, Professor of Physiology, Medicine, and Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail dharder@mcw.edu

See related article, pages 962–969

Key Words: CYP450 • 20-HETE • hypertension • CYP4A2 • endothelial dysfunction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Given that the area of cytochrome P450 genetics (CYP P450) is relatively new and is now experiencing an exponential rise in publications, it will be helpful to give some historical perspective relative to this editorial. With respect to arachidonic acid (AA) metabolism, we know most about the first two pathways of AA metabolism—cyclooxygenase (COX) and lipoxygenase enzymes—which metabolize AA to 5-,12-, and 15-hydroxyeicosatratetraenoic acid (HETE), prostaglandins, prostacyclin, thromboxane, and leukotrienes. These molecules modulate peripheral vascular function, regulate vascular tone, act as cytokines, and function in inflammatory processes.^1–4 Approximately 20 years ago manuscripts began emerging which defined a third pathway for AA metabolism and metabolite formation. This pathway was via formation of particulate, inducible, cytochrome-linked proteins.^5,6 Unlike the COX and leukotriene pathways, this system involved literally hundreds of genes, clustered into families, many of which had been previously studied as xenobiotic enzymes of drug metabolism in the liver and kidney. This third pathway was first studied by Capdevila,⁶ Oliw,⁷ and a number of others. AA was metabolized by cytochrome enzymes with an absorption spectra of 450 nM and labeled as the cytochrome P450 (CYP P450) pathway of AA metabolism. Since that time, well over a thousand articles have been published defining the physiologic functions of CYP P450 AA metabolites. These initial reports were largely ignored, however, and over the last decade a great deal of attention has been given to these metabolites, which function as receptor ligands and signaling molecules governing a variety of vascular phenomenon. The Figure depicts the three . . . [Full Text of this Article]

Related Article:

Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus

Ji-Shi Wang, Harpreet Singh, Frank Zhang, Tsuneo Ishizuka, Huan Deng, Rowena Kemp, Michael S. Wolin, Thomas H. Hintze, Nader G. Abraham, Alberto Nasjletti, and Michal Laniado-Schwartzman
Circ. Res. 2006 98: 962-969. [Abstract] [Full Text] [PDF]

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