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Vascular biology

Old-timer makes a comeback

Nature volume 396, pages 213–216 (1998)Cite this article

Edwards et al. now suggest both an identity (K+) for, and antagonists (ouabain and barium ions) against, EDHF. In proposing K+ as EDHF, they ensure the comeback of an old-timer in local regulation of vascular diameter7. Their results could explain earlier work showing that Na+-K+ exchanges contribute to the responses of isolated arteries to acetylcholine8, and the authors revamp the image of ouabain as a remarkable inhibitor that blocks the action of EDHF3 but not that of NO9,10. But there are still questions as to whether ouabain is selective, and whether its effect is truly due to inhibition of Na+-K+ exchanges, particularly in rat tissues. Another problem with ouabain, not to mention barium, is that use in vivo will be extremely limited. So, we still await a molecule that inhibits the production or action of EDHF with the same power and selectivity as L-NMMA.

Before we celebrate the identification of K+ as the universal EDHF, there are several other questions to be answered. First, can endothelial cells release enough K+ to be transferred across the existing diffusion barriers, such as the basal membrane and elastic laminae, on its way to the smooth muscle? How much K+ is involved, and can it be generated by the thin monolayer of endothelial cells? And is this plausible in thick-walled arteries such as the human coronaries11? Edwards et al. briefly report impalement experiments with K+-sensitive electrodes, but one must take their word for this (as they provide no real clues to allow others to reproduce their measurements), and accept that they have managed the tour de force of successfully inserting an electrode into the space between the endothelium and the media.

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Figure 1: Relaxation of vascular smooth muscle cells by diffusable vasodilator substances from endothelial cells.
Figure 2: Geography of research into enothelium-derived hyperpolarizing factors (EDHFs).

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  1. the Institut de Recherches Internationales Servier, 6 Place des Pliades, 92415, Courbevoie Cedex, France

    Paul M. Vanhoutte

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Vanhoutte, P. Old-timer makes a comeback. Nature 396, 213–216 (1998). https://doi.org/10.1038/24261

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