Evaluation of NOx in the cardiovascular system: relationship to NO-related compounds in vivo.

Diverse attention should be paid to evaluating NOx (NO2- and NO3-) in plasma as an index of endothelial nitric oxide (NO) formation in vivo. Nitric oxide, which subsequently appears as NOx, originates from different types of NO synthase and from nonenzymatic reactions. NOx also comes from exogenous sources such as food and gastrointestinal microorganisms. The fate of the NO incorporated into activation of guanylate cyclase, formation of nitrosyl hemoglobin (or nitrosohemoglobin), nitrosothiols, peroxynitrite and its derivatives and other possible compounds is not clear at present. However, some of these compounds would produce NOx as by-products or as final products through metabolism. Therefore, plasma NOx contains information about these pathways, although how extensively these factors contribute to plasma NOx has not been quantitatively defined. A theoretical simulation of NOx in the systemic circulation indicates that only small changes are expected by inhibition or stimulation of endothelial NO production. Measuring NOx production during coronary circulation has the advantage that some degree of NOx accumulation is expected from intact endothelial cells because an excretion system is absent in the heart.