Nitrite and Nitrate
in Human Health
and Disease

The short-lived, free radical molecule nitric oxide (NO) has emerged as one of the most versatile cell

signaling transmitters produced by mammalian biological systems. NO, identified as “endothelium-
derived relaxing factor” and proclaimed “Molecule of the Year” in 1992, functions critically in physi-
ology, neuroscience, and immunology. The vascular effects of NO alone include vasodilatation,

inhibition of platelet aggregation and leukocyte adhesion to the endothelium, scavenging of superox-
ide anions, and inhibition of smooth muscle cell hyperplasia. Early studies on NO stemmed from

work with nitroglycerin in an attempt to elucidate the mechanism through which it relieved pain due
to angina pectoris. It was discovered that the formation of NO from nitroglycerin accounts for its
therapeutic efficacy for angina by dilating constricted and diseased blood vessels in the heart. Not

surprisingly, some of the most prevalent diseases result, at least in part, from decreased NO availabil-
ity, for example, hypertension, atherosclerosis, diabetes mellitus, and hypercholesterolemia.

The discovery of the formation of NO from the semi-essential amino acid l-arginine through one
of three isoforms of nitric oxide synthase provided a key therapeutic target, which is still the focus of

much research today. Dietary supplementation of l-arginine has been shown to enhance NO produc-
tion in healthy individuals (despite already saturated extracellular concentrations), and this may both

provide cardiovascular protective effects and enhance athletic performance. Indeed, endothelial dys-
function, an early sign of cardiovascular disease, has been reversed through enhanced NO production.

This observation leads us to believe that intervention through the NO pathway is a viable route for
treatment and prevention of vascular dysfunction.