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(Circulation Research. 2008;102:1148.)
© 2008 American Heart Association, Inc.

Editorials

The EDHF Story

The Plot Thickens

Helena C. Parkington, Marianne Tare, Harold A. Coleman

From the Department of Physiology, Monash University, Clayton, Australia.

Correspondence to Prof Helena C. Parkington, Department of Physiology, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia. E-mail helena. parkington@med.monash.edu.au

See related article, pages 1247–1255

Key Words: EDHF • K_Ca2.3 • K_Ca3.1 • Na/K ATPase • endothelium

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

The dilator function of the vascular endothelium is critical for optimal tissue perfusion, and this is brought into stark reality in a number of diseases, such as hypertension, diabetes, and preeclampsia, in which endothelium-dependent vasodilator function is impaired. Prostacyclin and nitric oxide (NO) were the earliest identified endothelium-dependent vasodilators, but it was soon found that in many vascular beds, particularly in resistance vessels, vasorelaxation persisted when production of these autacoids was suppressed. This residual vasorelaxation was invariably associated with hyperpolarization of the vascular smooth muscle and the entity was dubbed "endothelium-derived hyperpolarizing factor" (EDHF).¹ From the outset, the identity of EDHF has been the subject of vigorous debate. Nonetheless, that the "EDHF effect" is blocked by agents that target calcium-activated K⁺ channels is among the few aspects of EDHF on which there is apparent consensus. There was also the debate on the significance, or otherwise, of EDHF. Is it just the poor cousin of NO, stepping into the breech when the latter is compromised, especially under conditions of enhanced oxidative stress? Then a beacon of light shone out from Japan, with the demonstration that EDHF assumed greater importance as vessel diameter decreased.² This was a key observation, supporting the importance of EDHF in the region of the vascular system where resistance is primarily determined. This was hotly followed by the revelation that EDHF may be targeted in diseases, diabetes,^3–5 hypertension,⁶ and apolipoprotein E-deficient mice.⁷ Thus, EDHF, suggested to provide vasodilation when NO was compromised, was also under attack in disease. . . . [Full Text of this Article]

Related Article:

Modulation of Endothelial Cell K_Ca3.1 Channels During Endothelium-Derived Hyperpolarizing Factor Signaling in Mesenteric Resistance Arteries

Kim A. Dora, Nicola T. Gallagher, Alister McNeish, and Christopher J. Garland
Circ. Res. 2008 102: 1247-1255. [Abstract] [Full Text] [PDF]