1El Research Advances Series Endothelium-Derived Relaxing Factor and Coronary Vasospasm

T he vascular endothelium is the monolayer of squamous cells in direct contact with the circulating blood. Since the first report in 1980 by Furchgott and Zawadzkil of the endothelium-dependency of the relaxation to acetylcholine in isolated arteries, an overwhelming number of find-ings have indicated that this most intimal layer of cells importantly modulates the degree of contrac-tion of the underlying vascular smooth muscle.2-4 It does so by liberating vasoactive substances, such as prostacyclin, a nonprostanoid endothelium-derived relaxing factor (EDRF),2 a hyperpolarizing sub-stance (endothelium-derived hyperpolarizing fac-tor, EDHF),5 and two constrictor substances (endothelium-derived contracting factors, EDCFs)6 (Figure 1). More and more data are emerging sug-gesting that alterations in endothelium-dependent responsiveness of vascular smooth muscle are involved in the pathogenesis of several cardiovas-cular diseases (see Vanhoutte7'8 for reviews). Coronary vasospasm plays an important pathoge-netic role, not only in variant angina but also in a wide spectrum of ischemic heart disease.9,10 Because coronary vasospasm can be provoked by several stimuli with different mechanisms of action that do not induce a pathologic response in normal subjects,11"2 a local nonspecific hypersensitivity of the coronary artery appears to be involved. This interpretation is in agreement with the clinical obser-vations that coronary vasospasm almost invariably occurs at atherosclerotic portions, although the extent of the coronary artery narrowing varies widely. Among the possible vascular components contributing to the spasm,13 the endothelium may play an important role. This brief review describes the current status of experimental and clinical stud-ies concerning the possible role of EDRFs under normal conditions and in the pathogenesis of coro-nary vasospasm