Nitric oxide physiological roles

Adams DR, Brochwicz-Lewinski M, Butler AR. Nitric oxide Physiological roles, biosynthesis and medical uses. Progr Chern Org Nat Prod 1999 76 1-186. 

Nitric oxide (NO) is a gaseous cellular messenger that transmits information between cells and within cells. In spite of its physiological role, NO is also a reactive species which is capable of reacting with biological molecules, and... 

Denitrification involves the sequential formation of nitrite, nitric oxide, and nitrous oxide. Two aspects of nitric oxide have attracted attention (a) chemical oxidation of biogenic nitric oxide to Nq, in the context of increased ozone formation (Stohl et al. 1996) and (b) the physiological role in mammalian systems (Feldman et al. 1993 Stuehr et al. 2004), in parasitic infections (James 1995), and in the inhibition of bacterial respiration (Nagata et al. 1998). Nitric oxide may be produced microbiologically in widely different reactions such as... 

First described in the 1980s as "endothelium-derived relaxing factor," nitric oxide (NO) is a vasodilator believed to play a role in regulation of blood pressure under physiologic and pathophysiological conditions. For example, inhibition of NO synthesis under normal conditions and during septic shock results in a significant elevation of blood pressure. 

S / V CONTENTS Preface, Robert W. Hay. Structure and Function of Manganese-Containing Biomolecules, David C. Weather-bum. Repertories of Metal Ions as Lewis Acid Catalysts in Organic Reactions, Junghan Suh. The Multicopper-Enzyme Ascorbate Oxidase, Albrecht Messerschmidt. The Bioinorganic Chemistry of Aluminum, Tomas Kiss and Etelka Farkas. The Role of Nitric Oxide in Animal Physiology, Anthony R. Butler, Frederick Flitney and Peter Rhodes. Index. 

While several studies reported that PLB was present in smooth muscle, very little was known about its role in Ca2+ handling. Some evidence suggested that in addition to A-kinase pathway phosphorylation, activation of the G -kinase pathway was associated with PLB phosphorylation. The latter was of particular interest to vascular smooth muscle, for which endothelium-dependent relaxation via nitric oxide (NO) made the mechanism of G-kinase-mediated relaxation of considerable physiological significance (Karczewski et al 1998). 

Nitric oxide is important to a wide variety of mammalian physiological processes (1,2), beyond being a constituent of air pollution (3). Natural physiological activities are now known to include roles in blood pressure control, neurotransmission and immune response, and a number of disease states involving NO imbalances have been reported (2,4) as the result of extensive research activity into the chemistry, biology and pharmacology of NO. Understanding the fundamental reaction mechanisms... 

N-diazeniumdiolates spontaneously dissociate at physiological pH to release nitric oxide (NO) by stable first order kinetics with half-lives ranging from 2 s to 20 h [209, 210]. They are blessed with many attributes that make them an especially attractive starting point for designing solutions to important clinical problems, namely they are stable as solids, have structural diversity, a controlled rate of release of NO on hydrolysis, and a rich derivatization chemistry that facilitates targeting of NO to specific sites of need, a critical goal for therapeutic uses of a molecule with natural bioeffector roles in virtually every organ [208]. 

Knowing that nitric oxide and hyaluronic acid both play an important role in the wound healing process, Di Meo et al. chose to combine the properties of both entities and synthesized new NO-donors based on hyaluronic acid derivatives exhibiting a controlled NO-release under physiological conditions (in vitro tests). These derivatives were fully characterized by and 13C NMR spectroscopy and their NO release monitored by means of UV spectrophotometric measurements.47... 

Like nitric oxide, the discovery of the eicosanoid signalling molecules was a significant event in twentieth century physiology, due largely to research led by Sir John Vane (Nobel Prize 1982). The diverse actions of the eicosanoids include roles in muscle contraction, blood coagulation, salt and fluid homeostasis, inflammatory responses and pain sensitivity. 

NO (molecular weight = 30) is small but plays a big role in physiological regulation, not least in the vasculature where its effects were first seen (see Chapter 4). Endothelium-derived relaxation factor (EDRF) was discovered its ability to cause dilatation of vessels by relaxing the arterial muscle layer. Only much later was EDRF discovered to be a gas, nitric oxide. More recent interest in NO is based on the evidence that it is antiatherogenic. The pathogenesis of atherosclerosis is complex but many of the known effects of NO can be implicated in this common and serious condition. 

Nitric oxide, NO, plays a number of roles in human physiology, including acting as a smooth muscle relaxant. Several drugs employed in clinical medicine act by supplying or increasing the levels of NO. 

Even though nitric oxide is the physiological mediator of a variety of responses, excess nitric oxide is toxic to many cells as a result of its role in the production of per-oxynitrite and resultant lipid oxidation. Inhibitors of the NOS enzyme are in clinical trials for the treatment of hypotension associated with septic shock. Administration of low concentrations of nitric oxide through respiratory ventilators has been implemented to treat persistent pulmonary hypertension of the newborn. 

The physiological importance of nitric oxide should also be mentioned. It plays an important role in smooth muscle relaxation, platelet inhibition, neurotransmission, immune regulation, and penile erection (Nobel Prize in 1998 for the discovery of its role in the cardiovascular system). The importance of NO in biological systems stimulated the development of electrochemical sensors and the investigation of the electrochemical behavior of that compound. 

The CNS contains a substantial amount of nitric oxide synthase (NOS), which is found within certain classes of neurons. This neuronal NOS is an enzyme activated by calcium-calmodulin, and activation of NMDA receptors, which increases intracellular calcium, results in the generation of nitric oxide. Although a physiologic role for nitric oxide has been clearly established for vascular smooth muscle, its role in synaptic transmission and synaptic plasticity remains controversial. Perhaps the strongest case for a role of nitric oxide in neuronal signaling in the CNS is for long-term depression of synaptic transmission in the cerebellum. 

Nitrogen monoxide, also known as nitric oxide, NO, is a precursor to nitrate fertilizers and a common atmospheric pollutant, but it also plays a multitude of vital roles in our human biology. Use nitric oxide as a keyword in your Internet search engine to find a plethora of websites devoted to the many roles this small but important molecule plays in our physiology and in various diseases, such as Alzheimer s, Parkinsons, asthma, heart disease, and infections. 

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