Molecular mechanisms underlying the role of nitric oxide in the cardiovascular system.

In the cardiovascular system, nitric oxide (NO) is involved in the short and long-term regulation of haemodynamics, and in a number of their pathological alterations. Investigation into the biochemistry of NO-synthase isoforms has confirmed that they also all produce superoxide anion (O(*)). The free radical NO can interact with many targets on which novel information has been recently obtained. The major results of these interactions are not only the well known activation of guanylyl cyclase, but also the formation of potentially cytotoxic peroxynitrite (ONOO(-)), and the formation of S-nitrosothiols and non-haem iron-dinitrosyl dithiolate complexes. Tissue O(2), O(*), low molecular weight thiols and transition metals (especially FeII) play a pivotal role in directing NO towards targets responsible for biological effects, or storage or release from these stores. In addition, circulating forms of NO have been proposed with S-nitrosation of blood proteins. All these mechanisms provide potential pharmacological targets for future therapeutic strategies.