DG: From isolated vessels to the catheterization laboratory: Studies of endothelial function in the coronary circulation of humans. Circulation

that an intact endothelium must be present for acetylcholine to relax isolated vessels. This was subsequently found to be true for many other vasoactive substances.2-6 As a result of work from several laboratories, this response has been shown to occur because the endothelium releases a short-lived nonprostanoid compound or family of com-pounds collectively termed the "endothelium-See p 458 and p 466 derived relaxing factor " (EDRF).7,8 These sub-stances relax vascular smooth muscle by activating guanylate cyclase9,10 and by producing transient smooth muscle hyperpolarization.11 The role of EDRF in regulating vascular tone was first impli-cated in large vessels but has now been extended to the microcirculation.12,13 Identity of Endothelium-Derived Relaxing Factor The chemical identity of EDRF has been the subject of intense investigations. Many of EDRF's biologic activities are shared by nitric oxide.14 These include the ability to activate guanylate cyclase, inhibition of platelet aggregation, short biologic half-life, and inactivation by hemoglobin. In 1987, Palmer et al15 reported that nitric oxide is synthesized and released by cultured endothelial cells and that EDRF may be nitric oxide. The evidence for nitric oxide being the sole EDRF is far from conclusive, however. The amount of nitric oxide released from cultured endothelial cells is insufficient to account for all of the vaso-dilator activity of EDRF simultaneously released The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association