PREFACE Nitric oxide (nitrogen monoxide, NO), a gaseous molecule, is derived from the amino acid, L-arginine, in the human body. Its discovery was a great surprise because other hormones and regulators in the body are made up of proteins, lipid-derived compounds, and other molecules, none of which are gaseous. NO affects a number of enzyme systems and binds to heme, a cofactor in some important enzymes. In many ways, NO acts as a hormone and regulates many processes. Its activities are generally beneficial. For example, it is a powerful generator of vasodilation by suppressing vascular smooth muscle contraction. Its action is rapid as it remains in the blood for only seconds. In other activities, NO inhibits platelet aggregation and the adhesion of leukocytes to endothelia. Poorly functioning pathways involving NO are hallmarks in patients with various diseases, such as diabetes, atherosclerosis, and hypertension. Consequently, nitric oxide becomes a substance of interest in therapeutic applications. Many of the properties and actions of this new regulator, nitric oxide, are reviewed in this volume. Reviews in this book have been ordered by first introducing the basic aspects of nitric oxide followed by chapters that involve clinical concepts. Accordingly, the first chapter is on the “Regulation of nociceptive transduction and transmission by nitric oxide” by A. Bavencoffe, S.-R. Chen, and H.-L. Pan. The next offering is by Z. Guo and D.A. Geller entitled “microRNA and human inducible nitric oxide synthase.” “Heart mitochondrial nitric oxide synthase: a strategic enzyme in the regulation of cellular bioenergetics” is authored by T. Zaobornyj and L.B. Valdez. W.P. Gray and A. Cheung review “Nitric oxide regulation of adult neurogenesis.” “Nitric oxide in the nervous system: biochemical, developmental, and neurobiological aspects” is the work of M. Cossenza, R. Socodato, C.C. Portugal, I.C.L. Domith, L.F.H. Gladulich, T.G. Encarnac¸a˜o, K.C. Kalaza, H.R. Mendonc¸a, P. Campello-Costa, and R. Paes-de-Carvalho. Y. Hu and D.-Y. Zhu report on “Hippocampus and nitric oxide.” “Nitric oxide and hypoxia signaling” is a review by H.S.J. Man, A.K.Y. Tsui, and P.A. Marsden. M.A. Hough, G. Silkstone, J. Worrall, and M.T. Wilson discuss “NO binding to the proapoptotic cytochrome c–cardiolipin complex.” S.F. Kim writes on “The nitric oxide-mediated regulation of prostaglandin signaling in medicine.”

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“Nitric oxide as a mediator of estrogen effects in osteocytes” is the topic of J. Joshua, H. Kalyanaraman, N. Marathe, and R.B. Pilz. In aspects related to disease conditions, contributions begin with “Insights into the diverse effects of nitric oxide on tumor biology” by D. Vasudevan and D.D. Thomas. A.H. Zea, A. Aiyar, and D. Tate review “Dual effect of interferon (IFNγ)-induced nitric oxide on tumorigenesis and intracellular bacteria.” Next, B.E. Sansbury and B.G. Hill cover the “Anti-obesogenic role of endothelial nitric oxide synthase.” H. Girouard and S.N. Tabatabaei report on “Nitric oxide and cerebrovascular regulation.” Then, C. Vecoli reports on “Endothelial nitric oxide synthase gene polymorphisms in cardiovascular disease.” The “Role of nitric oxide in pathophysiology and treatment of pulmonary hypertension” by P. Kruzliak, J. Maruyama, and K. Maruyama is the final chapter. The cover illustration is Fig. 14.2 of Chapter 14. Helene Kabes and Mary Ann Zimmerman of Elsevier, Oxford, UK were instrumental in the processing of these chapters. GERALD LITWACK North Hollywood, California May 8, 2014