Isotopic investigation of nitric oxide metabolism in disease

Y.C. Luiking*, N.E.P. Deutz

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE OF REVIEW: Nitric oxide is an important mediator of both physiological and pathophysiological processes. Nitric oxide is produced during direct conversion of arginine to citrulline. Nitric oxide is rapidly metabolized, mainly to nitrite/nitrate, and finally excreted as urinary nitrate. For that reason, plasma and urinary nitrite/nitrate have been measured frequently as indicators of nitric oxide production, but it is becoming clear that these methods only give qualitative data. More recently, stable isotope methods have been introduced for quantitative measurement of nitric oxide production. This review aims at summarizing and evaluating these isotopic investigations of nitric oxide metabolism in disease. RECENT FINDINGS: Different stable isotope methods are used to measure whole body nitric oxide production in vivo. These methods are all based on infusion of guanidino-labeled L-arginine and subsequent measurement of labeled products (e.g. nitrite/nitrate or citrulline). Nitric oxide synthesis in healthy individuals is found to be in the range of 0.2-1.0 micromol kg h, only 0.5-1% of arginine production. In diseased states, nitric oxide synthesis was found to be either decreased or increased. Increased nitric oxide synthesis was observed in gastroenteritis patients and in some animal models of sepsis. In patients with renal failure, however, both increased and decreased nitric oxide production have been reported. Nitric oxide production was not changed in familial hypercholesterolemia patients and after typhoid vaccination. SUMMARY: Using stable isotopes to measure whole body nitric oxide production in vivo is the most accurate method to study quantitative changes in the nitric oxide production rate. This technique is easy to perform in both healthy and diseased individuals, requiring infusion of stable isotopes for only a few hours and blood sampling.
Original languageEnglish
Pages (from-to)103-108
JournalCurrent Opinion in Clinical Nutrition and Metabolic Care
Issue number1
Publication statusPublished - 1 Jan 2003

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