Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanism to Clinical Implications
Julio A. Panza, MD, and Richard O. Cannon, III, MD. 320 pp. Armonk, NY: Futura Publishing Co, Inc; 1999. $75.00. ISBN 0-87993-436-0.
Nitric oxide (NO) is an endogenous vasodilator, which was described initially as endothelium-derived relaxing factor (EDRF) by Dr. Robert F. Furchgott. In 1978, he performed an experiment in his laboratory in New York that would lead to his realization that the presence of the endothelium is essential for the vasodilatory effect of acethylcholine. Twenty years after this key experiment, the Nobel prize was awarded to Dr. Furchgott (among others) for the discovery of EDRF. In Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanism to Clinical Implications, which was divided into 4 sections, the first chapter of the first section starts with a review of the discovery, biological roles, and regulation of endothelial NO by Dr. Furchgott himself. This chapter might be a valuable historical reference for anyone interested in this field.
Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanism to Clinical Implications is a multiauthored exploration of endothelial cell function, NO, and atherosclerosis, focusing on physiology, biology, histology, and clinical therapy. The first section of the book deals with the discovery, biological roles, and regulation of endothelial NO; the second with the basic mechanisms that lead to endothelial dysfunction in cardiovascular diseases; the third with the clinical studies of impaired endothelial function in patients with different cardiovascular conditions; and the fourth with the most important therapeutic strategies that have been developed to ameliorate endothelial dysfunction. The chapters are, in general, written authoritatively and laid out clearly. Of particular note in the first section is the chapter “Discovery of Biological Roles of Nitric Oxide in the Cardiovascular System” by Dr. Moncada and Dr. Higgs, which describes how the discovery of the l-arginine:NO pathway had a great impact on our understanding of the physiology and pathophysiology of the cardiovascular system and led the way to novel therapies for the treatment and prevention of cardiovascular diseases. The section ends with the chapter “Hormonal Regulation of Endothelium-Derived Factors,” which reviews the interesting experimental data suggesting that estrogens modulate the production and release of endothelium-derived factors and the response of vascular smooth muscle to them. Although this area has been largely ignored, it is certainly of great importance when attempting to understand cardiovascular diseases and hypertension.
In the second section, there is a review of recent studies related to the basic mechanisms leading to endothelial dysfunction in cardiovascular diseases. The chapter by Dr. Vanhoutte deals with the evidence for reduced release of EDRF from regenerated endothelial cells in balloon injured–porcine coronary arteries and also described the relation between NO and other factors: cyclooxygenase, endothelial-derived hyperpolarizing factor, oxidized-LDL, endothelin (ET)-1, angiotensin-converting enzyme, and bradykinin. The other chapters describe the potential roles of the most important endothelium-derived vasoconstrictor, ET-1, and vasodilator, NO, in human diseases including hypertension, atherosclerosis, coronary artery disease, congestive heart failure, and pulmonary hypertension. Furthermore, James K. Liao reviews the experimental evidence for the 3 distinct NO synthases (NOSs): neuronal NOS (type 1), inducible NOS (type 2), and endothelial NOS (type 3). He also focuses on the stabilization and enhancement of the proinflammation transcription factor nuclear factor–κB by NO. Of course, the impact of cytokine interaction and oxidant stress on the vasculature as well as of angiotensin II and NO are well covered. The third section deals with studies of endothelial dysfunction in patients with different cardiovascular conditions, including hypertension, hypercholesterolemia, coronary disease, and chronic heart failure. Julio A. Panza reviews the evidence for endothelial dysfunction in hypertension and the mechanisms of diminished NO activity in patients with essential hypertension and atherosclerosis. The chapter “Endothelial Vasodilator Dysfunction in Chronic Heart Failure” reviews the role of cytokines, NO, and the renin-angiotensin system in the vascular abnormalities associated with heart failure. The final section of the text describes therapeutic strategies to improve endothelial dysfunction and reviews acute and prolonged estrogen therapy in postmenopausal women, angiotensin-converting enzyme inhibition in coronary patients, NO therapy in cardiovascular diseases, and the effects of endothelial-derived NO as an antiatherogenic molecule. All these chapters are clearly written, relatively comprehensive, and up to date.
In summary, Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanism to Clinical Implications is an extremely valuable book and generously illustrated with excellent color histological photographs as well as black and white figures. It will be of considerable interest and value to all those interested in hypertension and cardiovascular disease, both treatment and prevention, including research scientists. This book will serve both as a comprehensive review for basic vascular scientists and clinicians as well as medical students and trainees who wish to become acquainted with the study of endothelial regulation of vascular physiology. Furthermore, it is an all but indispensable guide because it is both comprehensive and easy to use. Every medical library should possess a copy, and it should be on the bookshelf of every physician responsible for patients with hypertension and cardiovascular disease.