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(Circulation. 2005;111:724-727.)
© 2005 American Heart Association, Inc.

Editorial

The Endothelium-Derived Hyperpolarizing Factor Puzzle

A Mechanism Without a Mediator?

Richard A. Cohen, MD

From the Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Richard A. Cohen, MD, Director, Vascular Biology Unit, X708, Dept of Medicine, Boston University School of Medicine, 650 Albany St, Boston, MA 02118. E-mail racohen@bu.edu

Key Words: Editorials • endothelium • vasodilation

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

	Introduction

 
The article by Scotland et al¹ published in this issue of Circulation reports on a unique mouse model that might help to identify a longstanding, intensely investigated, and controversial substance called endothelium-derived hyperpolarizing factor (EDHF). EDHF is a "holy grail," a "third factor" that provides local control of vascular homeostasis in addition to nitric oxide (NO) and prostacyclin. The discovery of the latter substances, which are known to cause both hyperpolarization and relaxation, led to Nobel prizes. But beware acronyms! The term EDHF is >15 years old, and as yet no one substance and no one mechanism has been proposed that explains all of its features. The story of the investigation has been a meandering one, with many stops along the way. Each stop has taught us how blood vessels function, but there is more to be learned if we are to have a complete understanding.

See p 796

Twenty-five years ago, Robert Furchgott identified that acetylcholine and bradykinin generated a diffusible, short-lived mediator from endothelial cells that relaxed underlying smooth muscle cells by a mechanism similar to that of nitrovasodilators.² This seminal observation led to the identification of the substance as NO, contributed in a major way to the growth of vascular biology,³ and increased our understanding of why cardiovascular risk factors and disease diminish vasodilatation. Notwithstanding the importance of NO and cyclic guanosine monophosphate (cGMP), the major intracellular mediator of NO-induced smooth muscle relaxation, many of us in the field have had the nagging feeling that something was . . . [Full Text of this Article]

Related Article:

Investigation of Vascular Responses in Endothelial Nitric Oxide Synthase/Cyclooxygenase-1 Double-Knockout Mice: Key Role for Endothelium-Derived Hyperpolarizing Factor in the Regulation of Blood Pressure in Vivo

Ramona S. Scotland, Melanie Madhani, Sharmila Chauhan, Salvador Moncada, Jørgen Andresen, Holger Nilsson, Adrian J. Hobbs, and Amrita Ahluwalia
Circulation 2005 111: 796-803. [Abstract] [Full Text]

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