The potential role of the red blood cell in nitrite-dependent regulation of blood flow.

Nitrite was once thought to have little physiological relevance. However, nitrite is now being increasingly recognized as a therapeutic or possibly even physiological precursor of nitric oxide (NO) that is utilized when needed to increase blood flow. It is likely that different mechanisms for nitrite bioconversion occur in different tissues, but in the vascular system, there is evidence that erythrocyte haemoglobin (Hb) is responsible for the oxygen-dependent reduction of nitrite to modulate blood flow. Here, we review the complex chemical interactions of Hb and nitrite and discuss evidence supporting its role in vasodilation. We also discuss ongoing work focused on defining the precise mechanisms for export of NO activity from red blood cells and of other pathways that may mediate nitrite-dependent vasodilation.