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(Circulation Research. 2006;98:1344.)
© 2006 American Heart Association, Inc.

Editorials

COX-2, Another Important Player in the Nitric Oxide–Endothelin Cross-Talk

Good News for COX-2 Inhibitors?

Ulrich Hink, Thomas Münzel

From the Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany.

Correspondence to Thomas Münzel MD, II.Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany. E-mail tmuenzel@uni-mainz.de

See related article, pages 1439–1445

Key Words: COX-2 • endothelin • prostanoids

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

Traditionally, the role of the endothelium was thought to be primarily that of a selective barrier to the diffusion of macromolecules from the vessel lumen to the interstitial space. During the past 20 years, numerous additional roles for the endothelium have been defined such as regulation of vascular tone, modulation of inflammation, promotion as well as inhibition of vascular growth, and modulation of platelet aggregation and coagulation. Endothelial dysfunction is a characteristic feature of patients with cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and chronic smoking. More recent studies indicate that it may predict long-term atherosclerotic disease progression as well as cardiovascular event rate.¹ There is a growing body of evidence that decreased endothelial bioavailability of nitric oxide (NO^·) in particular attributable to increased production of reactive oxygen species, such as superoxide (O₂^·–), leads to an activation of the renin–angiotensin system,^2,3 increased formation of cyclooxygenase (COX)-dependent vasoconstrictors,⁴ but also to increased expression of the most potent endogenous vasoconstrictor endothelin-1 (ET-1).^5–9

Of the 4 active endothelins (ET-1 to ET-4) ET-1 is the predominant isoform in the cardiovascular system. ET-1 exerts its major cardiovascular effects through activation of 2 distinct G protein–coupled receptors, the ET_A and ET_B receptors. ET_A receptors are found exclusively in smooth muscle cells. Endothelin-1 promotes vasoconstriction, mitogenesis, and thrombosis predominantly via binding to the ET_A receptor. ET_B receptors are localized to some extent in smooth muscle cells, but also in endothelial cells. Activation of ET_B receptors has been demonstrated to cause the release of . . . [Full Text of this Article]

Related Article:

Increased Expression of Cyclooxygenase-2 Mediates Enhanced Contraction to Endothelin ET_A Receptor Stimulation in Endothelial Nitric Oxide Synthase Knockout Mice

Yingbi Zhou, Srabani Mitra, Saradhadevi Varadharaj, Narasimham Parinandi, Jay L. Zweier, and Nicholas A. Flavahan
Circ. Res. 2006 98: 1439-1445. [Abstract] [Full Text] [PDF]

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				F. Syeda, E. Tullis, A. S. Slutsky, and H. Zhang Human neutrophil peptides upregulate expression of COX-2 and endothelin-1 by inducing oxidative stress Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2769 - H2774. [Abstract] [Full Text] [PDF]