OBJECTIVES: We investigated whether plasma nitros(yl)ated species(RXNOs) that mediate systemic nitric oxide(NO) bioactivity are depleted in individuals with cardiovascular risk factors and endothelial dysfunction. BAC...
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OBJECTIVES: We investigated whether plasma nitros(yl)ated species(RXNOs) that mediate systemic nitric oxide(NO) bioactivity are depleted in individuals with cardiovascular risk factors and endothelial dysfunction. BACKGROUND: Endothelium- derived NO acts not only as a regional messenger but exerts significant systemic effects via formation of circulating RXNOs delivering NO to sites of impaired production. METHODS: Endothelial function was assessed in 68 patients with one to four major cardiovascular risk factors(RF) and 39 healthy control subjects(C) by measurement of flow- mediated dilation(FMD) of the brachial artery using high- resolution ultrasound. In parallel, plasma RXNOs were determined by reductive gas phase chemiluminescence. RESULTS: Increasing numbers of risk factors were accompanied by a progressive decrease in FMD: 6.5± 0.4% (C); 4.7± 0.5% (one RF); 2.8± 0.4% (two RF); 2.2± 0.4% (three RF); and 1.0± 0.3% (four RF). Progressively impaired vascular function was associated with a concomitant decrease in plasma RXNOs(p< 0.01): 39± 2 nmol/l(C); 30± 2 nmol/l(one RF); 24± 3 nmol/l(two RF); 22± 3 nmol/l(three RF); and 15± 2 nmol/l(four RF), with univariate correlation between FMD and RXNO(r=0.41, p< 0.001). In a multivariate regression model, RXNO was an independent predictor of endothelial function. CONCLUSIONS: Endothelial dysfunction in patients with cardiovascular risk factors is associated with decreased levels of circulating RXNOs. Plasma RXNOs may be diagnostically useful markers of NO bioavailability and a surrogate index of endothelial function. Whether the observed decrease in concentration reflects impaired NO formation, accelerated decomposition, and/or consumption of RXNOs and whether these processes play a causal role in the pathophysiology of arteriosclerosis remain to be investigated.
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