Nitric Oxide and Cyclooxygenases

Abstract

Nitric oxide (NO), derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in acute and chronic inflammatory events. In view of the complexity associated with the inflammatory response, the dissection of possible mechanisms by which NO modulates this response will be profitable in designing novel and more efficacious NOS inhibitors. Besides the NOS system, cyclooxygenase (COX), the enzyme that converts arachidonic acid (AA) to the prostaglandins (PG) prostacyclin (PGI2) and thromboxane A2 (TXA2), is another important enzyme in a variety of inflammatory diseases. An important property pertinent to the role of NO in inflammation that was recently discovered in our laboratories is its ability to activate COX, resulting in significant production of proinflammatory PG. This discovery led to the demonstration that dual inhibition of the release of proinflammatory NO and PGs contributes to the antiinflammatory properties of NOS inhibitors. I will present evidence that COX enzymes are targets for the pathophysiological roles of NO and that, once activated in the presence of NO, these represent important transduction mechanisms for the actions of NO.