[Physiology and in vivo measurements of nitric oxide in man]

Nitric oxide (NO) is a simple molecule, highly conserved across species with important effects on several physiological mechanisms. In the cardiovascular system, NO is tonically released by the endothelial cells in response to shear stress to maintain vascular tone. This effect is due to the relaxation of the vascular smooth muscle cells in the medium layer (tunica media) of the arterial wall. However, NO is also involved in the regulation of synaptic neurotransmission, platelet aggregation, inflammation, appetite, peristalsis, renal metabolism, respiratory function, lipid metabolism and glucose metabolism. Therefore, an abnormal production of NO (over- or under-production) has multi-systemic effects. Metabolic disorders like hypertension, obesity or dyslipidaemia are associated with a reduction of NO production. The mechanisms responsible for a decreased NO synthesis are partially known but oxidative stress, overproduction of endogenous inhibitors of the Nitric Oxide Synthase (NOS) such as asymmetric dimethylarginine (ADMA) and genetic factors may be implicated. The half-life of NO is extremely short in biological samples (t1/2 < or = 0.2 sec) and its in vivo measurement is very difficult. Therefore, indirect methods have been developed to measure the end products of NO metabolism in biological samples. Some of these methods have used stable isotopes to trace the metabolic fate of the precursor of NO (Arginine) and measure the appearance of stable isotopes in the end products [nitrate (NO3), nitrite (NO2), citrulline]. However, the existing methods are expensive, invasive and require complex analytical laboratory techniques.