Nitric Oxide in Physiology and Medicine

NO is a gas at room temperature, with a low solubility in water (10 M). From aqueous solution it is rapidly lost to the headspace. In oxygenated water it is oxidized slowly, at a rate which it is critically concentration-dependent, to nitrite (equations 1-3), At this stage no nitrate is formed. However, in oxygenated water and particularly in certain biological media such as blood, nitrite is rapidly oxidized to nitrate.  

NO is a radical species, but unlike most other radicals, it is not particularly reactive. However, it does react very rapidly with iron to give well authenticated iron-nitrosyls. Reaction with iron is responsible for the activation of guanylate cyclase it may also be responsible for the cytotoxicity of NO and it has been incorporated into a number of analytical procedures for the detection and quantitation of NO. 

NO has high diffusion rates in both aqueous and lipid media, and travels rapidly between cells and across phospholipid membranes. It has a biological half-life of less than a minute and on oxidation forms relatively stable anions. This instability in vivo reflects reactions with oxygen, superoxide and haemoglobin, and these reactions limit the volume through which NO can travel to exert influence.  

The low molecular weight of NO may allow rapid movement in aqueous environments. Molecules larger than NO have much lower diffusion coefficients and rates of spread. Models to describe the kinetic and concentration profiles for NO have been developed, based on diffusion models used to describe heat conduction in solids. These models show NO concentrations to be a function of the rate of formation, diffusion coefficient, distance from the source and time. Close to a production source, perhaps within a radius of 10/rm, concentrations reach a steady state within a few hundred ms of release. This is an order of magnitude faster than the measured biological half-life of NO, so that metabolism of NO in vivo should not significantly affect these concentration gradients 

Unfortunately, some of the same physiochemical characteristics make quantitation of NO difficult. Most studies in vivo and in vitro have used indirect indices of NO production such as breakdown products of NO metabolism, second messengers, or biological events in effector systems. Recent developments in probe technology and mass spectrometry have allowed the direct detection of NO in some situations. Constitutive NO synthases (cNOS) in vascular endothelium and other tissues produce small quantities of NO for continuous maintenance of vascular tone and cellular communication. Inducible NO synthases (iNOS) are induced by immunological stimuli such as interleukins and lipopolysaccharides, and synthesize relatively large amounts of NO for long periods. In general, therefore, it is much more difficult to study constitutive than inducible NO production. 

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Butler, A. Rhodes, P. Nitric Oxide in Physiology and Medicine In Uses of Inorganic Chemistry in Medicine, Farrell, N., Ed. The Royal Society of Chemistry Cambridge, 1999, pp 58-76. 

The discoverers of nitric oxide as a signal transmitter in the mediation of a variety of important cellular functions, in particular in the cardiovascular system, R. F. Furchgott, F. Murad, and L. J. Ignarro, were awarded the 1998 Nobel Prize in Physiology and Medicine. 

Research into the role played by NO in biological systems is an active area, and in 1992, Science named NO Molecule of the Year . The 1998 Nobel Prize in Physiology or Medicine was awarded to Robert F. Furchgott, Louis J. Ignarro and Ferid Murad for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system (http //www.nobel.se/medicine/laureates/1998/press.html). 

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