EDITORIAL COMMENT Endothelium: A New Target for Cardiovascular Therapeutics*

During the past two decades, it has been well established that vascular endothelium plays a pivotal role in maintaining vascular tone. It is of interest to note that the initial discovery of endothelial-dependent vasodilation by Furchgott and Zawadzki (1) in 1980 occurred as a result of an accidental finding due to an error of a research assistant. In their seminal paper, Furchgott and Zawadzki (1) reported that the thoracic aorta and a variety of other arteries obtained from experimental animals exhibited relaxation in response to acetylcholine (ACh) only if the endothelium was intact (1). Subsequent investigations in their laboratory revealed that ACh stimulated the release of a diffusible relaxing substance from endothelial cells, later referred to as endothelium-derived relaxing factor (EDRF) (2). It was not until 1986 that Furchgott and coworkers, as well as Ignarro et al., independently proposed that EDRF is nitric oxide (NO) (3,4). The discovery of NO and other mediators released by the endothelium has subsequently led to tremendous interest of investigators in this field throughout the world. During the last 10 years, we have seen an exponential growth in our knowledge and understanding of the role of endothelial dysfunction in a variety of cardiovascular conditions (5–20). It has been demonstrated that endothelial dysfunction might indeed be the initiating event in the process of atherosclerosis and vascular remodeling, which subsequently leads to clinical coronary artery disease (CAD) (21,22). Accordingly, there has been an ongoing, aggressive search for therapeutic choices suitable for reversing endothelial dysfunction with the hope that such therapeutic intervention, if instituted early in the course of the disease, might prevent and/or modify the subsequent risk of clinical disease and related cardiac events (6–25). The magnitude of interest in this area can be best illustrated by the large number of articles published on the endothelium and related issues from 1997 to 1999. A recent Medline search revealed that, on average, during this period in excess of 1,200 articles per year were published in the English language regarding investigations dealing with vascular endothelium in humans, and, of these, nearly 550 articles specifically describe the effects of various cardiovascular therapeutic agents on the endothelium. Indeed, the time has come to recognize the endothelium as an important and new target for cardiovascular therapeutics. The article by Anderson et al. (26) in this