Reference values for serum nitric oxide metabolites in an adult population

https://doi.org/10.1016/j.clinbiochem.2009.09.011Get rights and content

Abstract

Objectives

To determine reference values for serum nitric oxide metabolites (nitrite + nitrate = NOx) concentrations in adult subjects.

Design and methods

Serum NOx concentration was measured, using the Griess method, in 694 non-smoking apparently healthy subjects, randomly selected from a population-based study. The International Federation of Clinical Chemistry guidelines and the robust method were used for determining reference values.

Results

The 95% reference values for serum NOx concentration and serum NOx/creatinine ratio were 11.5 to 76.4 μmol/L and 0.111 to 0.729 in men and 10.1 to 65.6 μmol/L and 0.121 to 0.777 in women, respectively. With increasing body mass index, upper limits of serum NOx and the NOx/creatinine ratio increased in women and decreased in men. Serum NOx levels above upper limits predicted both diabetes and metabolic syndrome in women.

Conclusions

This study reports the first set of reference values for serum NOx concentration and NOx/creatinine ratio in a relatively large healthy non-smoking population.

Introduction

Nitric oxide (NO), discovered as a vasodilator in the late 1970s, is now considered to be a ubiquitous molecule [1]. In recent years, interest in the measurement of serum nitric oxide metabolites (nitrite + nitrate = NOx), as a surrogate for NO production, has increased [2]. Changes in serum NOx concentrations have been reported in several pathological states including diabetes [3], [4], metabolic syndrome [4], [5], hypertension [6], and heart failure [7]; in addition NO has been introduced as a marker for predicting survival in elderly [8].

Despite reports on the usefulness of serum NOx measurement in clinics [6], [7], the normal range or reference values of serum NOx have not yet been determined. A reference interval is the interval between, and including the lowest and highest values [9], and is the most widely used medical decision-making tool [10].

To the best of our knowledge, since there is no study addressing reference values for serum NOx concentration in a large healthy population, the aim of the present study was hence to determine sex- and age-specific reference values for serum NOx concentration in adult subjects.

Section snippets

Subjects

Study participants (n = 3505) were chosen from among participants randomly selected for the Tehran Lipid and Glucose Study (TLGS) [11] during 2006 and 2007. Excluded were smokers (smoked ≥ 1 cigarette per day or using waterpipe), pregnant and menopausal women, obese [body mass index (BMI) ≥ 30 kg/m2] and hypertensive subjects [blood pressure ≥ 140/90 or using antihypertensive drugs], participants with dyslipidemia [triglycerides (TG) ≥ 1.7 mmol/L, total cholesterol (TC) ≥ 5.17 mmol/L, or using

Results

Although serum NOx values lacked normal distribution, distribution of data was approximated to normal after Box-Cox transformation, as shown in Fig. 1; a similar pattern was observed for serum NOx/Cr ratio. The normality of transformed values was confirmed by tests of normality (i.e. Kolmogrov–Smirnov and Shapiro–Wilk tests).

Table 1 shows the baseline characteristics of the study subjects. Compared to women, men were older and had significantly higher WC, WHR, systolic and diastolic blood

Discussion

Reference values for serum NOx concentrations have been investigated and are presented in this study for both genders and different age groups using current standards in a large healthy sample of adults. The reference range for serum NOx in normal subjects was 10.3 to 66.8 μmol/L. These values may be useful considering the wide range of physiopathological states in which NO metabolism changes.

It has been suggested that measurement of serum NOx levels may facilitate monitoring the health status

Acknowledgments

This work was supported by a grant (No. 177) from the Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences. The authors thank Professor Paul S. Horn who provided software for determining reference values with robust method. Technical Assistance by Ms. V. Khorasani and linguistic help by Ms. N. Shiva are appreciated.

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