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(Circulation. 2005;111:5-7.)
© 2005 American Heart Association, Inc.

Editorial

Cytochrome P-450 Under Pressure

More Evidence for a Link Between 20-Hydroxyeicosatetraenoic Acid and Hypertension

Ingrid Fleming, PhD

From the Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany.

Correspondence to Ingrid Fleming, PhD, Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. E-mail fleming@em.uni-frankfurt.de

Key Words: Editorials • cytochrome P-450 enzyme system • hypertension • kidney • vasoconstriction

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

Considerable evidence links the metabolism of arachidonic acid by cytochrome P-450 (CYP) enzymes with the regulation of vascular tone and homeostasis as well as renal function. The enzymes in question fall into 2 classes: the epoxygenases, which generate vasodilator epoxyeicosatrienoic acids (EETs), and the /-1 hydroxylases, which generate the constrictor 20-hydroxyeicosatetraenoic acid (20-HETE).

See p 63

EETs act as endothelium-derived hyperpolarizing factors, and alterations in their formation and tissue levels contribute to the development of some forms of hypertension.¹ For example, in spontaneously hypertensive rats (SHR) and in rats with angiotensin II–induced hypertension, inhibitors of the soluble epoxide hydrolase, which increase EET levels, markedly attenuate blood pressure; additionally, salt-induced hypertension in salt-sensitive Dahl rats has been linked with a failure to increase EET production.² Moreover, a polymorphism of the CYP 2J2 epoxygenase, which results in the attenuated binding of the transcription factor Sp1 and reduced promoter activity, has been associated with an enhanced risk of developing coronary artery disease in humans.³ However, there is also evidence suggesting that a CYP 2C epoxygenase expressed in endothelial cells is able to generate superoxide anions (O₂^–) in addition to EETs⁴ and in patients with coronary artery disease the inhibition of CYP 2C–derived O₂^– formation can markedly improve acetylcholine-induced vasodilatation in the forearm vasculature.⁵

When one searches for links between CYP expression and cardiovascular disease, it is perhaps more logical to look for changes in the production of a CYP-derived vasoconstrictor, in particular 20-HETE, which is currently characterized as a prohypertensive metabolite . . . [Full Text of this Article]

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Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension

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Circulation 2005 111: 63-69. [Abstract] [Full Text]

Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension

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