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It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start.
The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.
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The aim of this treatise is to summarize the current understanding of the mechanisms for blood flow control to skeletal muscle under resting conditions, how perfusion is elevated (exercise hyperemia) to meet the increased demand for oxygen and other substrates during exercise, mechanisms underlying the beneficial effects of regular physical activity on cardiovascular health, the regulation of transcapillary fluid filtration and protein flux across the microvascular exchange vessels, and the role of changes in the skeletal muscle circulation in pathologic states. Skeletal muscle is unique among organs in that its blood flow can change over a remarkably large range. Compared to blood flow at rest, muscle blood flow can increase by more than 20-fold on average during intense exercise, while perfusion of certain individual white muscles or portions of those muscles can increase by as much as 80-fold. This is compared to maximal increases of 4- to 6-fold in the coronary circulation during exercise. These increases in muscle perfusion are required to meet the enormous demands for oxygen and nutrients by the active muscles. Because of its large mass and the fact that skeletal muscles receive 25% of the cardiac output at rest, sympathetically mediated vasoconstriction in vessels supplying this tissue allows central hemodynamic variables (e.g., blood pressure) to be spared during stresses such as hypovolemic shock. Sympathetic vasoconstriction in skeletal muscle in such pathologic conditions also effectively shunts blood flow away from muscles to tissues that are more sensitive to reductions in their blood supply that might otherwise occur. Again, because of its large mass and percentage of cardiac output directed to skeletal muscle, alterations in blood vessel structure and function with chronic disease (e.g., hypertension) contribute significantly to the pathology of such disorders. Alterations in skeletal muscle vascular resistance and/or in the exchange properties of this vascular bed also modify transcapillary fluid filtration and solute movement across the microvascular barrier to influence muscle function and contribute to disease pathology. Finally, it is clear that exercise training induces an adaptive transformation to a protected phenotype in the vasculature supplying skeletal muscle and other tissues to promote overall cardiovascular health. Table of Contents: Introduction / Anatomy of Skeletal Muscle and Its Vascular Supply / Regulation of Vascular Tone in Skeletal Muscle / Exercise Hyperemia and Regulation of Tissue Oxygenation During Muscular Activity / Microvascular Fluid and Solute Exchange in Skeletal Muscle / Skeletal Muscle Circulation in Aging and Disease States: Protective Effects of Exercise / References
A classic nephrology reference for over 20 years, Seldin & Giebisch's The Kidney, is the acknowledged authority on renal physiology and pathophysiology. The fourth edition follows the changed focus of nephrology research to the study of how individual molecules work together to affect cellular and organ function, emphasizing the mechanisms of disease. With over 40 new chapters and over 1000 illustrations, this edition offers the most in-depth discussion anywhere of the physiologic and pathophysiologic processes of renal disease. Comprehensive, authoritative coverage progresses from molecular biology and cell physiology to clinical issues regarding renal function and dysfunction. If you research the development of normal renal function or the mechanisms underlying renal disease, Seldin & Giebisch's The Kidney is your number one source for information.* Offers the most comprehensive coverage of fluid and electrolyte regulation and dysregulation in 51 completely revised chapters unlike Brenner & Rector's The Kidney which devotes only 7 chapters to this topic.* Includes 3 sections, 31 chapters, devoted to regulation and disorders of acid-base homeostasis, and epithelial and nonepithelial transport regulation. Brenner & Rector's only devotes 5 chapters to these topics.* Previous three editions edited by Donald Seldin and Gerhard Giebisch, world renowned names in nephrology. The title for the fourth edition has been changed to reflect their considerable work on previous editions and they have also written the forward for this edition. * Over 20 million adults over age 20 have chronic kidney disease with the number of people diagnosed doubling each decade making it America's ninth leading cause of death.
New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.
A vast literature has been concerned with arteriosclerosis and yet, many aspects of pathogenesis and of the mechanism of development of the arteriosclerotic vascular lesion remain only poorly understood. In recent years, our knowledge of the earliest stages of arteriosclerosis have greatly improved. By now, we have learned to relate morphologic changes to disturbances in function. It has been of particular impor tance that components of the arterial wall could be analyzed in regard to dysfunction, for example, in the endothelium or the vascular smooth muscle. The interaction of the different morphological components of the vascular wall could thus be much bet ter understood. Likewise, the interaction between the arterial wall and the flowing blood could be much better described, including the intimate relationship between platelets and the endothelium, the coagulation system and the endothelium, the granulocytes and the endothelial cell layer, as well as processes of migration of blood cells into the subendothelial space. The recognition of functional and morphological disturbance has attained clinical significance not only because the arteriosclerotic diseases have quantitatively reached the dimensions of an epidemic, that is, of a magnitude never been witnessed. It is also because of the development of new drugs that interfere with the atherogenic process and thereby prevent the development of the disease or halt its progression. It is also becoming increasingly possible to inhibit the occurrence of complications in existing arteriosclerotic lesions in manifest disease, i. e.
Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in the pathophysiology of diseases, such as atherosclerosis, diabetes and hypertension, and these entities are responsible for the largest part of cardiovascular mortality and morbidly. Over the last decade major new discoveries and concepts involving the endothelium have come to light. This important reference collects this data in an easy to reference resource. Written by known experts, and covering all aspects of endothelial function in health and disease, this reference represents an assembly of recent knowledge that is essential to both basic investigators and clinicians. - Provides a complete overview of endothelial function in health and diseases, along with an assessment of new information - Includes coverage of groundbreaking areas, including the artificial LDL particle, the development of a new anti-erectile dysfunction agent, a vaccine for atherosclerosis, coronary calcification associated with red wine, and the interplay of endoplasmic reticulum/oxidative stress - Explores the genetic features of endothelium and the interaction between basic knowledge and clinical syndromes