Synopsis

The field of nitric oxide (NO) research has developed in explosive proportions since the discovery of naturally occurring NO in 1986. The biological importance of NO was first suggested by the observations that the drug nitroglycerin widens the blood vessels and lowers blood pressure by liberating NO directly in the blood vessel. NO was shown to work by elevating the tissue levels of another signaling molecule known as cyclic GMP.

These observations were quickly followed by those demonstrating that NO inhibits blood clotting by interfering with platelet function, again via the actions of cyclic GMP. The cyclic GMP system represents the principal signal transduction mechanism by which NO elicits many of its physiological effects in the mammalian species. More recently, however, cyclic GMP-independent pathways have been discovered which can account for certain biological actions of NO. The most important is the alteration of certain proteins and consequent modification of protein function. This mechanism may be important in both physiological and pathophysiological actions of NO. NO plays important regulatory roles not only in blood vessels per se but also in the peripheral nervous system, where NO is the principal neurotransmitter of the nerves that communicate with various tissues including the erectile tissue. The neurotransmitter NO produces a cyclic GMP-dependent relaxation of smooth muscle in erectile tissue, thereby promoting erectile function. NO may function in a similar way also in the gastrointestinal tract to facilitate the movement of ingested contents, and in the airways to promote breathing.

Based on these properties of NO, new drugs can be developed for the treatment of hypertension, stroke, angina pectoris, heart failure, vascular complications of diabetes, gastrointestinal ulcers, impotency and other vascular disorders. An excellent example of the application of basic information learned about NO has been the development of sildenafil or Viagra, which has revolutionized the treatment of impotency, one of the most prevalent disorders in the world.

NO elicits many other actions in mammalian systems including inhibition of cell growth, antibacterial effects, other anti-infectious effects, and also promotes learning and memory as well as smell and taste. There are undoubtedly many as yet unknown functions of NO. This allows for an extensive opportunity to develop novel drugs for the diagnosis, prevention and treatment of a multitude of cardiovascular and other disorders such as gastrointestinal ulcers and inflammatory bowel disease.