Nitric oxide regulation of eicosanoid production

The nitric oxide and cyclooxygenase pathways share a number of similarities. NO is the mediator generated from the nitric oxide synthase (NOS) pathway. Cyclooxygenase (COX), converts arachidonic acid to the prostaglandins (PG), prostacyclin (PGI2) and thromboxane A2 (TXA2). Two major forms of NOS and COX have been identified to date. Under normal circumstances, the constitutive isoforms of these enzymes are found in virtually all organs. Their presence accounts for the regulation of several important physiological effects (e.g. antiplatelet activity, vasodilation, cytoprotection). On the other hand, in an inflammatory setting, these enzymes are induced in a variety of cells resulting in the production of large amounts of pro-inflammatory and cytotoxic NO and PG. Release of NO and PG by these enzymes has been associated with the pathological roles of these mediators in several disease states. An important link between the NOS and COX pathways was made in 1993 by Salvemini and coworkers [1]. They demonstrated that nitric oxide activated the COX enzymes, leading to overt production of PGs. This in turn exacerbated the inflammatory response. Such studies raised the possibility that COX enzymes might represent important endogenous “receptor” targets for the multifaceted roles of NO [1].