Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.7.1.4 (nitrite reductase)
 1,847 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) regulates normal vasomotor tone and modulates important homeostatic functions such as thrombosis, cellular proliferation, and adhesion molecule expression. Recent data implicate a critical function for hemoglobin and the erythrocyte in regulating the bioavailability of NO in the vascular compartment. Under normoxic conditions the erythrocytic hemoglobin scavenges NO and produces a vasopressor effect that is limited by diffusional barriers along the endothelium and in the unstirred layer around the erythrocyte. In hemolytic diseases, intravascular hemolysis releases hemoglobin from the red blood cell into plasma (decompartmentalizes the hemoglobin), which is then able to scavenge endothelial derived NO 600-fold faster than erythrocytic hemoglobin, thereby dysregulating NO homoestasis. In addition to releasing plasma hemoglobin, the red cell contains arginase which when released into plasma further dysregulates arginine metabolism. These data support the existence of a novel mechanism of human disease, hemolysis associated endothelial dysfunction, that potentially participates in the vasculopathy of iatrogenic and hereditary hemolytic conditions. In addition to providing an NO scavenging role in the physiological regulation of NO-dependent vasodilation, hemoglobin and the erythrocyte may deliver NO as the hemoglobin deoxygenates. Two mechanisms have been proposed to explain this principle: 1) Oxygen linked allosteric delivery of S-nitrosothiols from S-nitrosated hemoglobin (SNO-Hb), and 2) a nitrite reductase activity of deoxygenated hemoglobin that reduces nitrite to NO and vasodilates the human circulation along the physiological oxygen gradient. The later newly described role of hemoglobin as a nitrite reductase is discussed in the context of hypoxic vasodilation, blood flow regulation and oxygen sensing.
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PMID:Role of the red blood cell in nitric oxide homeostasis and hypoxic vasodilation. 1708 90

Vascular disease, a significant cause of morbidity and mortality in the developed world, results from vascular injury. Following vascular injury, damaged or dysfunctional endothelial cells and activated SMCs engage in vasoproliferative remodeling and the formation of flow-limiting intimal hyperplasia (IH). We hypothesized that vascular injury results in decreased bioavailability of NO secondary to dysregulated arginine-dependent NO generation. Furthermore, we postulated that nitrite-dependent NO generation is augmented as an adaptive response to limit vascular injury/proliferation and can be harnessed for its protective effects. Here we report that sodium nitrite (intraperitoneal, inhaled, or oral) limited the development of IH in a rat model of vascular injury. Additionally, nitrite led to the generation of NO in vessels and SMCs, as well as limited SMC proliferation via p21Waf1/Cip1 signaling. These data demonstrate that IH is associated with increased arginase-1 levels, which leads to decreased NO production and bioavailability. Vascular injury also was associated with increased levels of xanthine oxidoreductase (XOR), a known nitrite reductase. Chronic inhibition of XOR and a diet deficient in nitrate/nitrite each exacerbated vascular injury. Moreover, established IH was reversed by dietary supplementation of nitrite. The vasoprotective effects of nitrite were counteracted by inhibition of XOR. These data illustrate the importance of nitrite-generated NO as an endogenous adaptive response and as a pathway that can be harnessed for therapeutic benefit.
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PMID:Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. 2143 78