Nitric oxide (NO) generated from L-arginine by NO synthases in the endothelium and in other cells plays a central role in several aspects of vascular biology and has been linked to many regulatory functions in mammalian cells. Whereas for a long time the signaling actions of NO in the vasculature have been thought to be short-lived as a result of the rapid reaction of NO with hemoglobin, recent studies changed the biochemical thinking of NO. NO is not anymore the paracrine agent with only local effects, but, like a hormone, it disseminates throughout the body. Thus, a circulating pool of NO exists, opening new considerable pharmacological and therapeutical avenues in the diagnosis and therapy of cardiovascular diseases. In this review we briefly discuss the major routes of NO metabolism and transport in the mammalian circulation, considering plasma, red blood cell and tissue compartments separately, with a special focus on the implication of the circulating NO pool in clinical research.

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