The gaseous free radical nitric oxide is an abundant intracellular messenger molecule that plays a central role in maintenance of health, and is heavily involved in signal transduction in various cells of the body . This molecule acts as a mediator in the regulation of cardiac function as well as having an important role in regulating contractility of the heart and maintenance of vascular tone in the cardiovascular system. As one of the most significant individuals in our discovery of nitric oxide, Dr. Robert Furchgott pioneered our understanding of this molecule through his experiments on the vasorelaxant properties of acetylcholine and the subsequent proposal of the presence of the endothelium derived relaxing factor, which was later identified to be nitric oxide . Given the observation that cardiovascular disorders are the number one cause of death in many nations around the world, research into the vasorelaxant properties seems particularly relevant in order to help combat rising rates of vascular hypertension and high blood pressure. In this paper, the properties of nitric oxide are discussed largely with respect to the cardiovascular system. This paper focuses on the synthesis and characteristics of nitric oxide, the mechanisms of action by which nitric oxide works and the regulation of nitric oxide in the body, and finally a short summary of Robert Furchgott’s contributions to the discovery of nitric oxide and its properties.
Synthesis of nitric oxide
Nitric oxide is a gaseous, diatomic molecule that plays an important role as a mediator of cardiac function, working largely as a vasodilator in the cardiovascular system. Nitric oxide is synthesized by a family of enzymes known as nitric oxide synthases (NOSs) which catalyze the transformation of the amino acid L-arginine to L-citrulline in the body . Nitric oxide synthases use 1.5mol of NADPH and 2mol of O2 in the presence of flavin mononucleotide and other compounds to oxidize a nitrogen from L-arginine to produce nitric oxide, and as a by-product, citrulline . There are 3 main isoforms of NOS present in the body, neuronal NOS (nNOS), endothelial NOS (nNOS), and inducible NOS (iNOS), all three of which are coded for by different genes present on different chromosomes, but they do share similar characteristics in cofactor binding regions and electron transfer regions of the enzymes [7, 12]. All three isoforms have, at their amino terminals, a heme group which is linked to the middle of the protein by a calmodulin-binding domain, and upon binding of calmodulin, electron flow is initiated from the flavin mononucleotide to the heme group, thus promoting conversion of L-arginine to nitric oxide and L-citrulline . The three isoforms are present at different locations in the body, as nNOS is primarily found in neurons and skeletal muscle cells, eNOS is primarily found in endothelial cells, particularly in the cardiovascular system, and iNOS is primarily found in...