ABSTRACT
Centre for Clinical Pharmacology, University College London, 140 Tottenham Court Road, London, W1P 9LN, UK Tel/Fax: 0171 209 6351; E-mail: a.hingorani@ucl.ac.uk
INTRODUCTION
In 1980 Furchgott and Zawadzki reported the observation that vascular relaxation induced by acetylcholine was dependent on the presence of the endothelial lining of the blood vessel (Furchgott and Zawadzki, 1980) If the endothelium was removed, the relaxation to acetylcholine was abolished whereas the contractile response to noradrenaline and the dilator response to glyceryl trinitrate were both preserved. Endothelium-dependent relaxation to acetylcholine was shown to be mediated by the release of an unstable, diffusible factor (endothelium-derived relaxant factor; EDRF) which had a biological half-life of a few seconds (Furchgott, 1984; Furchgott, 1990) Subsequently the dilator responses to a variety of other agonists including bradykinin, substance P, adenosine diphosphate, 5hydroxytryptamine, ß-agonists and certain neuropeptides were also shown to be endotheliumdependent and mediated by EDRF (Moncada et al., 1991). The release of EDRF was also shown to attenuate the response to certain endogenous vasoconstrictors (Martin et al., 1986).
