The Endothelium: Modulator of Cardiovascular Function [antikvár]

FOREWORD Advancements in the sciences depend in the main on the burgeoning of knowledge that follows a key discovery. The cardiovascular system is no exception, starting with the publication, in 1628, of William Harvey's classic text, Exercitatio Anatómica de Motu Cordis et Sanguinis in Animalibus. In more recent years much attention has been focused on the complex local events that govern the behavior of the blood vessels, including those at the sympathetic nerve terminals, the neuroeffector junction, the smooth muscle, and the endothelium. Again, one can cite key discoveries that focused the attention of investigators and sparked new information. For example, although Barger and Dale, in 1910, had observed that the substance that we now call norepinephrine causes responses more like those of sympathetic nerve stimulation than did epinephrine, it was the direct demonstration by von Euler in 1946 that the sympathetic nerves cause cardiovascular activation by release of norepinephrine from their endings that provided the key discovery. Other key advances included Axelrod's demonstration of the sympathetic neuronal membrane amine uptake mechanism and its importance, together with the role of catechol-O-methyl transferase, in the disposition of the released norepinephrine. Ahlquist's recognition of the presence of both a- and ß-adrenoceptors on blood vessels, and Sutherland's discovery of the second messenger, cyclic AMP. In the last 10 years, another explosion of knowledge has occurred following the observations by Furchgott and Zawadzki in 1980 that the relaxations of contracted isolated arteries by acetylcholine was mediated by the release of some relaxing factor from endothelial cells. This they called endothelium-derived relaxing factor (EDRF). This led, in 1986, to the proposal by Furchgott and by Ignarro, that this factor may be the radical nitric oxide. With the demonstration that there may be more than one EDRF, and that the endothelium can synthesize both vasodilator and vasoconstrictor substances (EDCF), the potential importance of local autocrine-paracrine mechanisms in circulatory control was evident. This has led to ongoing studies on the nature of EDRF and EDCF, the mechanisms of release, including the growing recognition of the importance of the guanine nucleotide binding proteins in signal transduction, the physiological role, and changes in the balance between EDRF and EDCF in pathological states, including reperfusion, hypertension, diabetes, hypercholesterolemia, atherosclerosis, and vasospasm. Thus, what started as a pharmacological observation has been increasingly relevant to the pathophysiology of cardiovascular diseases. Anyone, including those active in this area, understandably may feel like William Harvey, when he stated that he almost felt that the motion of the heart and blood was to be comprehended only by God. Fortunately, Dr. Lüscher and Dr. Vanhoutte, who, through their research, have contributed so much to present understanding of the role of endothelium in the regulation ofthe vascular system, have provided us with a comprehensive overview of present knowledge, written concisely and cleariy, with excellent illustrations to clarify key issues. The list of over 1000 references is a clear indication of the need for this book to provide all interested in the circulation, clinicians and scientists, students and teachers, with our current understanding ofthe role played by the endothelium in modulating cardiovascular function, both in health and disease. By their thorough analysis of current knowledge, they have provided the platform for those with ideas, determination, and ability to seek new horizons. John T. Shepherd, M.D., D.Sc. Mayo Clinic and Foundation Rochester, Minnesota