Nitric oxide: at the heart of the matter

Nitric Oxide and the Cardiovascular Systemedited by J.H. Loscalzo and J.A. VitaHumana Press, 2000. $175.00 (hardback) (vii + 616 pages)ISBN 0 89603 620 0The massive increase in the amount of research into the roles of nitric oxide (NO) in myriad biological processes is staggering, so much so, that it is essentially impossible to write all-encompassing review articles in this field. Recent years have seen several books devoted to the roles of NO in defined physiological or pathological processes, and one of the most recent, Nitric Oxide and the Cardiovascular System, is no exception.Although NO is without a doubt important in all aspects of physiology, in 1998 the Nobel Committee decided that NO was primarily a molecule of importance in the vasculature. A reader of this book will certainly come away with the impression that this deceptively simple molecule has a very complex chemistry, is a vasodilator key to the function of endothelial cells, modulates the function of cardiac myocytes, and might improve the function of transplanted organs. Furthermore, it is clear that novel strategies involving chemical NO donors and gene therapy are being suggested as possible solutions to intractable problems such as restenosis post-angioplasty or post-stenting, transplant rejection, acute respiratory distress syndrome and atherosclerosis.Nitric Oxide and the Cardiovascular System is organized into three broad sections: ‘Biology of Nitric Oxide’, ‘Cardiovascular Pathophysiology of Nitric Oxide’ and ‘Nitric Oxide in Cardiovascular Therapeutics’. The first section starts with the chemistry that underlies much of the fascinating biology of NO and is followed by a discussion of the cellular and molecular biology of nitric oxide synthases (NOS), the enzymes that produce NO in animals. These chapters are de rigueur in any book about NO and provide the basic information for those new to the NO field in addition to some recent updates. The book then begins its true focus on the cardiovascular effects of NO, with a chapter on signal transduction mediated by NO, which discusses the classical (and Nobel-Prize-winning) cGMP pathway stimulated by NO and more recent studies on nitrosylation of target signal transduction proteins. Subsequent chapters in the first section deal with the regulation of gene expression by NO, the roles of NO in apoptosis, the modulation of ion channels by NO, the control of vasomotor and platelet functions by NO, and the effects of NO on cardiac myocytes and fibroblasts.The second section, ‘Cardiovascular Pathophysiology of Nitric Oxide’, contains discussions of the relevance of NO to endothelial dysfunction, hypertension, atherosclerosis, thrombosis, heart failure, shock, stroke and ischemia–reperfusion injury. From these chapters it is clear that cardiovascular disease, the bane of Western civilization in the 21st century, might be associated directly with dysregulation of NO production. This assessment leads logically to the third section, ‘Nitric Oxide in Cardiovascular Therapeutics’, which contains chapters on therapies for restenosis, acute respiratory failure, tissue preservation for transplantation and atherosclerosis. These diseases might be amenable to therapy with chemical NO donors of various classes (administered directly or coated on implantable biomaterials), inhaled NO, l-arginine (the substrate for NOS), NOS gene therapy and/or antioxidants.The book might have been laid out more logically along the lines of the chemistry of NO (comprising the biological chemistry chapter as well as the chapters on nitrovasodilators, S-nitrosothiols and diazeniumdiolates), the cellular and molecular biology of NO, and the involvement of NO in cardiovascular pathophysiology and therapeutics. Such a division would lead the reader from the basic to the applied chemistry, to the in vitro effects of NO, and finally to whole animals and clinical studies. This minor quibble aside, Nitric Oxide and Cardiovascular Therapeutics is a well-written, comprehensive tome that represents the state of the art in this field.