The "vascular" origins of exhaled nitric oxide

The origin of an exhaled gas is a classical physiological question. The biology and chemistry of nitric oxide (NO) is complex. In physiological conditions, NO acts while dissolved in aqueous biological solutions [1]. At high picomolar concentrations, it causes relaxation of vascular smooth muscle [2]. This is a result of activation of intra-cellular soluble guanylyl cyclase that increases the concentration of cyclic guanosine monophosphate (cGMP) which in turn initiates relaxation [1]. The evidence that NO normally regulates pulmonary vascular resistance depends on two observations. Firstly, changes in resistance are seen with inhibition of the endothelial enzyme nitric oxide synthase (eNOS). Secondly, pulmonary vascular disease is associated with changes in NO production.