NO is a gaseous signalling molecule. It is a key vertebrate biological messenger, playing a role in a variety of biological processes. It is a known bioproduct in almost all types of organisms, ranging from bacteria to plants, fungi, and animal cells. Nitric oxide, known as an endothelium–derived relaxing factor (EDRF), is biosynthesized endogenously from L–arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to make nitric oxide. One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signalling molecule. Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signalling is deactivated. The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow. Sildenafil (Viagra) is a common example of a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances the signals that are the downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP–specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, allowing for the signal to be enhanced, and thus vasodilation. Another endogenous gaseous transmitter, hydrogen sulfide (H2S) works with NO to induce vasodilatation and angiogenesis in a cooperative manner.
Keywords: EDRF, NOS, NADPH, PDE5, cGMP, Q10, CoQ10, Nitric oxide, Nitrates, Nitrites, L–Arginine, Citrulline