PECULIARITIES OF NITROGEN MONOXIDE METABOLISM AGAINST THE BACKGROUND OF METABOLIC SYNDROME.

Abramova N.O., Suchko K.O.

Bukovinian state medical university, Ukraine

Introduction. Over the past decades problem of metabolic syndrome (MS) became extremely urgent. MS is associated with the development of vascular pathology. Obesity and insulin resistance, accompanied by aseptic inflammation, provoked by increased production of cytokines, leades to endothelial dysfunction. One of the mechanisms of endothelial dysfunction in patients with MS if imparement of nitrogen monoxide (NO) metabolism. It is known that NO is vasodilator and is synthesized by splitting from L-arginine by means of NO-synthase (NOS).

There are three types of NO-synthases, two of them are united under the name constitutional NOS - include neuronal (nNOS) and endothelial (eNOS), which are calcium-dependent and inducible (iNOS) which is activated by cytokines [1]. Elevation of cytokines expression is accompanied by activation of iNOS, which ensures production of NO in quantities that 1000 times higher than production of NO by constitutional NOS [1, 6]. However, for patients with impaired carbohydrate metabolism a number of processes that lead to inactivation of NO are typical. Excessive production of superoxide anion radical (O₂) is accompanied by decreased activity of eNOS. NO binds to other reactive oxygen species (ROS) with subsequent conversion to peroxynitrite, which has damaging effects on the endothelium [5, 8]. However peculiarities of disorders of NO metabolism in patients with MS is still poorly understood.

The aim of the study. To study the dependence of stable metabolites of nitric oxide levels on carbohydrate metabolism, degree and type of obesity in patients with metabolic syndrome.

Materials and methods. The study involved 63 patients with MS and 20 healthy persons in the control group.

Patients were divided into 3 groups: I - group - 28 obese patients with MS, II - group - 15 overweight patients with MS, III - 20 patients with MS with a body mass index below 25 kg / m².

The diagnosis of MS is established according to criteria of the World Diabetes Federation (IDF), based on anthropometric, clinical and laboratory methods of research [2].

Violations of carbohydrate metabolism were diagnosed according to WHO criteria (1999). To assess the degree of insulin resistance homeostasis model assessment of insulin resistance (HOMA-IR) was used. We considered that patient has insulin resistance if HOMA-IR was > 2.

Fasting glucose level was determined by glucose oxidase method, immunoreactive insulin (IRI) and C-peptide - using ELISA method.

The degree of obesity was determined using the body mass index (BMI), to diagnose the type of obesity waist to hip ratio was calculated (W / H).

Stable NO metabolites were determined by nitrite anion (NO₂) and nitrate anion (NO₃) levels in serum of venous blood by photocolorimetric method using Griess reagent [4].

Statistical analysis of the data was performed using the Student t-test and Pearson's rank correlation coefficient using software complex Statistica 6.0 for Windows.

Results and discussion. As a result of the study we have found significantly 39,3%, 74,5% and 98,8% higher levels of NO₂ in the group I compared with groups II and III, and group of healthy persons (p <0,05). Level of NO₂ was also significantly 2,76, 1,98 and 1,59 times higher in groups I, II and III group compared with healthy subjects (p <0,05).

Total value of NO metabolites - nitrites + nitrates (NO₂ + NO₃) in group I was 30,7% higher than in group III (p <0.05). Also, elevation of NO₂ + NO₃ in groups I, II and III was 1,96, 1,57 and 1,39 times higher than in healthy individuals (p <0.05).

These results confirm data on the growth of formation of nitrogen monoxide metabolites on the background of enhanced expression of cytokines, that in our study is due adipocytes, and is typical for patients with obesity.

As a result of correlation analysis positive correlation between the level of NO₂ and W / H (r = 0,389, p <0.05), HOMA-IR (r = 0,367, p <0.05), IRI (r = 0,468, p <0.05) and fasting glucose level (r = 0,375, p <0.05) has been revealed.

Positive correlation between total value nitrites + nitrates with W / H (r = 0,498, p <0.05), IRI (r = 0,448, p <0.05) and C-peptide (r = 0,472, p <0.05) has been found.

Encasement of NO metabolites production against weight gain by abdominal type, elevation of leptin level in blood and deepening the degree of insulin resistance has been found in our study. Level of the most active metabolite of nitrogen monoxide - NO₂ increased with the growth of hyperglycemia caused by insulin resistance, that provokes the development of aseptic inflammation [3].

Conclusions.

1. Production of stable metabolites of nitrogen monoxide increases in proportion to the body mass index in patients with abdominal type of obesity.

2. Elevation of stable metabolites of nitrogen monoxide in serum becomes more pronounced with the deterioration of carbohydrate metabolism.

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