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Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Schechter, Alan N. Gladwin, Mark T. |
| Copyright Year | 2006 |
| Abstract | The ability of oxyhemoglobin to inhibit nitric oxide (NO)-dependent activation of soluble guanylate cyclase and vasodilation provided some of the earliest experimental evidence that NO was the endothelium-derived relaxing factor (EDRF). The chemical behavior of this dioxygenation reaction, producing nearly diffusion limited and irreversible NO scavenging, presents a major paradox in vascular biology: The proximity of large amounts of oxyhemoglobin (10 mmol/L) to the endothelium should severely limit paracrine NO diffusion from endothelium to smooth muscle. However, several physical factors are now known to mitigate NO scavenging by red blood cell encapsulated hemoglobin. These include diffusional boundaries around the erythrocyte and a red blood cell free zone along the endothelium in laminar flowing blood, which reduce reaction rates between NO and red cell hemoglobin by 100- to 600-fold. Beyond these mechanisms that reduce NO scavenging by hemoglobin within the red cell, 2 additional mechanisms have been proposed suggesting that NO can be stored in the red blood cell either as nitrite or as an S-nitrosothiol (S-nitroso-hemoglobin). The latter controversial hypothesis contends that NO is stabilized, transported, and delivered by intra-molecular NO group transfers between the heme iron and beta-93 cysteine to form S-nitroso-hemoglobin (SNO-Hb), followed by hypoxia-dependent delivery of the S-nitrosothiol in a process that links regional oxygen deficits with S-nitrosothiol-mediated vasodilation. Although this model has generated a field of research examining the potential endocrine properties of intravascular NO molecules, including S-nitrosothiols, nitrite, and nitrated lipids, a number of mechanistic elements of the theory have been challenged. Recent data from several groups suggest that the nitrite anion (NO2-) may represent the major intravascular NO storage molecule whose transduction to NO is made possible through an allosterically controlled nitrite reductase reaction with the heme moiety of hemoglobin. As subsequently understood, the hypoxic generation of NO from nitrite is likely to prove important in many aspects of physiology, pathophysiology, and therapeutics. |
| Starting Page | 697 |
| Ending Page | 705 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/26/4/697.full.pdf |
| Alternate Webpage(s) | http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=75EB71E0442EB206D4D0FCD8C114E8BE?doi=10.1.1.534.4117&rep=rep1&type=pdf |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/26/4/697.full.pdf?download=true |
| PubMed reference number | 16424350v1 |
| Volume Number | 26 |
| Issue Number | 4 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anions Biochemistry Blood Cells Drug Allergy Erythrocytes Flow Guanylate Cyclase Heme Iron Hemoglobin C Disease Hypoxia Nitrite Reductase Oxygen Oxyhemoglobin device S-Nitrosothiols S-nitroso-N-acetylpenicillaminyl-glycine methyl ester S-nitrosohemoglobin SKIL protein, human Smooth muscle (tissue) Therapeutic brand of coal tar Therapeutic procedure millimole nitric oxide storage nitrite ion peptidyl-L-cysteine methyl disulfide biosynthetic process from peptidyl-cysteine physiological aspects soluble guanylyl cyclase |
| Content Type | Text |
| Resource Type | Article |
