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European Heart Journal 1985 6(1):37-49;
Copyright © 1985 by the European Society of Cardiology.
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© 1985 The European Society of Cardiology

Studies of endothelium-derived relaxant factor (EDRF), its nature and mode of action

T. M. GRIFFITH

Departments of Cardiology and Radiology, University of Wales College of Medicine Heath Park, Cardiff CF4 4XN

Received 1 February 1984; .

Abstract

The effect of endothelium on constrictor responses to 5-hydroxytryptamine, histamine, phenylephrine and actylcholine was studied and shown to be much greater in isolated perfused coronary arteries than aortic strips of the rabbit. Localised endothelial damage predisposed nonspecifically to ‘coronary spasm’. Endothelium-dependent dilatation was shown by bioassay to be mediated by a humoral agent, endothelium-derived relaxant factor (EDRF), with half-life of 6 s. Experiments with inactivating agents indicate that EDRF is not a cyclo-oxygenase or lipoxygenase product and not a free radical; they imply that it contains a carbonyl group at or near its active site. Experiments in which guanylate cyclase and cGMP phosophodiesterase were inhibited indicate that EDRF acts by elevating smooth muscle cGMP. Ergometrine was shown to stimulate EDRF activity which may be relevant to its clinical use in provoking coronary spasm. The physiological role and pathophysiological relevance of this novel, ubiquitous and potent endogenous vasodilator are not yet known; it may be of particular importance in modulating coronary vasomotor responses.

Key Words: Endothelium-derived relaxant factor (EDRF), • coronary arteries, • vasoconstrictors.


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