Article

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

Department of Pathology and Center for Free Radical Biology, University of Alabama, Birmingham, AL 35294, USA.
Cardiovascular Research (Impact Factor: 5.81). 10/2010; 89(3):507-15. DOI: 10.1093/cvr/cvq323
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Sulfide (H2S/HS-) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential (patho)physiology of the cross-talk between sulfide and NO has received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO-) and nitrosopersulfide (SSNO-). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivity of either species and discuss its possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide.
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