dehydrogenase enzymes. Gasotransmitters are under investigation in disciplines such as: biosensing, immunology, neuroscience, gastroenterology, and many other fields to include pharmaceutical development initiatives. While biomedical research has received the most attention, gasotransmitters are under investigation throughout biological kingdoms. Many analytical tools have been developed to assist in the study of gasotransmitters. Nitric oxide The 1998 Nobel Prize in Physiology or Medicine was awarded for the discovery of nitric oxide (NO) as an endogenous signaling molecule. The research emerged in 1980 when NO was first known as the 'endothelium-derived relaxing factor' (EDRF). The identity of EDRF as actually being NO was revealed in 1986 which many consider to mark the beginning of the modern era of gasotransmitter research. Relative to carbon monoxide and hydrogen sulfide, NO is exceptional due to the fact it is a radical gas. NO is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make NO ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule. It is a known bioproduct in almost all types of organisms, ranging from bacteria to plants, fungi, and animal cells. NO is biosynthesized endogenously from L-arginine by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to make NO. Independent of NOS, an alternative pathway coined the nitrate-nitrite-nitric oxide pathway, elevates NO through the sequential reduction of dietary nitrate derived from plant-based foods such as: leafy greens, such as spinach and arugula, and beetroot. For the human body to generate NO through the nitrate-nitrite-nitric oxide pathway, the reduction of nitrate to nitrite occurs in the mouth by the oral microbiome. The production of NO is elevated in populations living at high altitudes, which helps these people avoid hypoxia by aiding in pulmonary vasculature vasodilation. The endothelium (inner lining) of blood vessels uses NO to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow. NO contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Humans with atherosclerosis, diabetes, or hypertension often show impaired NO pathways. In the context of hypertension, the vasodilatory mechanism follows: NO acts through the stimulation of the soluble guanylate cyclase, which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes reuptake of Ca2+ and the opening of