NO in the cardiovascular system.

A focused issue on nitric oxide (NO) is timely within a studies of coronary endothelial dysfunction in humans. The year of the award of the Nobel Prize for Biology and development of atherosclerosis is one of the most imMedicine to the discovery of the fundamental roles of this portant long-term consequences of endothelial dysfunction. simple gas in cardiovascular physiology and pathophysiolJeremy and colleagues [9] review the current status of ogy. At the time of the seminal report by Furchgott and knowledge regarding the influence of NO in this process. Zawadzki of a labile endothelium-derived relaxing factor In the last several years, it has been recognised that NO (EDRF) responsible for acetylcholine-induced vasodilatinfluences not only the vasculature but also the myocaration [1], it could not have been imagined that the dium. Paulus and Shah [10] discuss the effects of NO on substance responsible would turn out to have such a cardiac diastolic function in experimental preparations and multiplicity of functions and effects, not just in the in patients, while Balligand [11] reviews the regulation of cardiovascular but also in many other systems. Our myocardial b-adrenergic responsiveness by NO. Rakhit knowledge about NO has indeed advanced enormously and Marber [12] present a review of quite recent data that since those early days. implicate NO in myocardial ischaemic preconditioning. This issue of Cardiovascular Research brings together Perhaps the main therapeutic advance that has been several review articles covering many of these advances, as developed as a direct result of research into NO is its use well as a selection of original articles that reflect continuin inhaled form to treat various pulmonary disorders; this ing studies in the field. Sessa and colleagues [2] review the is reviewed by Hayward [13]. Other aspects of NO are molecular biology of the NOSs, and the development of covered by additional review articles, while the original gene-modified mice as a powerful experimental tool for articles encompass a broad range of topical areas, and dissecting out the physiological and pathophysiological illustrate the potential for advance in the field. roles of NO. Andrew and Mayer [3] describe the enWe hope that this issue will provide a state-of-the-art zymatic function of the NOSs, while Fleming and Busse review of current knowledge, and will stimulate new [4] review the signal transduction of NOS activation. research to address some of the important questions and Leiper and Vallance [5] bring us up to date with the studies controversies identified herein. of endogenous inhibitors of the NOSs, compounds that may turn out to have important physiological and pathophysiological roles. The realisation that NO-depenReferences dent pathways may be modulated by angiotensin converting enzyme (ACE) has potentially far-reaching implica[1] Furchgott RF, Zawadski JV. The obligatory role of endothelial cells tions, not least with respect to therapeutic manipulations, in the relaxation of arterial smooth muscle by acetylcholine. Nature and this area is reviewed by Linz and colleagues [6]. Kojda 1980;288:373–376. and Harrison [7] describe the fundamental role of the [2] Papapetropoulos A, Rudic RD, Sessa WC. Molecular control of nitric oxide synthases in the cardiovascular system. Cardiovasc Res interactions between NO and reactive oxygen species in 1999;43:509–520. the genesis of endothelial dysfunction, and the in[3] Andrew PJ, Mayer B. Enzymatic function of NO synthases. volvement of these interactions in several pathological Cardiovasc Res 1999;43:521–531. processes. Clinical investigation has progressed alongside [4] Fleming I, Busse R. Signal transduction of eNOS activation. the advances in basic science, and Drexler [8] reviews Cardiovasc Res 1999;43:532–541.