Nitric oxide synthase Subject

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Markers of inflammation, especially CRP (measured with a highly sensitive technique, referred to as hs-CRP), have become the center of attention in recent years (22). This increased interest stems from several important observations made by Ridker and co-workers. Serum CRP has been shown to be an independent cardiovascular disease risk factor (23,24). High levels predict CAD death in healthy middle-aged men (25) and in patients with unstable CAD (26). In acute coronary syndromes, serum CRP concentrations correlate with the severity of endothelial dysfunction (27). In the CARE trial, subjects with elevated markers of inflammation (CRP and serum amyloid A > 90th percentile) were at high cardiovascular risk and responded best to pravastatin treatment in terms of cardiovascular risk reduction (28). The statin also reduced serum CRP concentrations (29). CRP co-incubated with LDL is readily taken up by macrophages, in contrast to native LDL, suggesting that CRP could promote foam cell formation (30). A link with endothelial dysfunction may be related to the fact that CRP decreases endothelial nitric oxide synthase (eNOS) expression and bioactivity in human aortic endothelial cells (31). 

Kingwell BA, Formosa M, Muhlmann M, Bradley SJ, McConell GK. Nitric oxide synthase inhibition reduces glucose uptake during exercise in individuals with type 2 diabetes more than in control subjects. Diabetes 2002 51 2572-2580. 

The measurement of total N02 and N03 in blood is an index of endothelial nitric oxide synthase activity (TessaroUo et al., 2015). Moreover, the high altitude subjects suffer from the reduction of N02 level in their blood, leading to several diseases at hypoxia conditions (Kim et al., 2003). Recent studies reported that the administration of N03 -rich beetroot juice to human and several animal models promotes NO-like... 

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