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Визир В.А., Волошина И.Н. Плазменное содержание маркеров симпатической нервной системы у больных гипертонической болезнью в сочетании с ож
13.05.2014, 22:53

Резюме
Визир В.А., Волошина И.Н. Плазменное содержание маркеров симпатической нервной системы у больных гипертонической болезнью в сочетании с ожирением.
В исследовании проведено определение плазменного содержания норадреналина и нейропептида Y у больных гипертонической болезнью в сочетании с ожирением. Показано, что концентрация нейропептида Y имеет нелинейную взаимосвязь с индексом массы тела. У больных с гипертонической болезнью ІІІ стадии отмечается наиболее выраженное нарушение секреции симпатических медиаторов.
Ключевые слова: гипертоническая болезнь, нейропептид Y, ожирение.
Резюме
Візір В.А., Волошина І.М. Плазмовий вміст маркерів симпатичної нервової системи у хворих на гіпертонічну хворобу у поєднанні з ожирінням.
У дослідженні проведено визначення плазмового вмісту норадреналіну і нейропептіду Y у хворих на гіпертонічну хворобу у поєднанні з ожирінням. Показано, що концентрація нейропептіду Y має нелінійний взаємозв'язок з індексом маси тіла. У хворих з гіпертонічною хворобою ІІІ стадії спостерігається найбільш виражене порушення секреції симпатичних медіаторів.
Ключові слова: гіпертонічна хвороба, нейропептід Y, ожиріння.
Summary
Vizir V.A, Voloshina I.N. Plasma levels of sympathetic nervous system mediators in hypertensive obese patients.
In this study plasma content of noradrenaline and neuropeptide Y in hypertensive obese patients had been determined. We revealed that concentration of neuropeptide Y had a nonlinear relationship with body mass index. The most severely impaired secretion of sympathetic neurotransmitters had beed observed in post-stroke hypertensive subjects.
Key words: hypertension, neuropeptide Y, obesity.

УДК 616.12-008.331.1-085.217

Запорожский государственный медицинский университет

пр. Маяковского, 26, 69035, г. Запорожье, Украина

Zaporozhye State Medical University

69035, Mayakovsky avenue 26, Zaporozhye, Ukraine

dr_voloshyna@mail.ru

Hypertension is one of the most prevalent diseases in the world [7]. Risk of hypertensive complications increases due to concomitant comorbid states and metabolic disorders. Obesity is the most mutual co-morbidity among hypertensive patients [1, 3-6]. Increased activity of the sympathetic nervous system (SNS) considered to b as a common pathogenetic factor in the hypertension progression and obesity [11]. Until now, intense researches has been devoted to searching of optimal diagnostic and prognostic markers of SNS activity using a variety of laboratory and imaging methods. Norepinephrine known as a mediator of the SNS activity with intermediate duration of action. Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that acts as a neurotransmitter in the brain and in the autonomic nervous system of humans; which is characterized by long-term effects, lasting up to several hours [10]. Compared with noradrenaline, NPY has a weak sympathomimetic activity, however, in the noradrenergic stimulated surrounding its effects could increased vastly [8]. Determination of the plasma content of sympathetic neurotransmitters in hypertensive obese patients, depending on body mass index (BMI) and stage of hypertension remained to be relavant.

Link to scientific programs, plans, themes. This study is part of the current research on department of internal diseases № 2 of Zaporozhye State Medical University "Pathogenetic, clinical and prognostic features of target organ damage in patients with cardiovascular disease and the development of new research areas of diagnostic, prevention and treatment» (№ public registration U 0108 005 117).

The aim of the study was to determine the plasma level of norepinephrine and neuropeptide Y in hypertensive obese patients.

Materials and methods. One hundred high-risk hypertensive patients (66 men, 44 women) aged 42-67 years, mean age 56 ± 2,8 years had been prospectively included in this study. Hypertension has been established according to the recommendations of the Ukrainian Association of Cardiology [7]. Fifty hypertensive patients had ischemic stroke in anamnesis. The control group consisted of 20 healthy normotensive volunteers (17 men and 15 women) aged 37-57 years, mean age 50 ± 4,2 years. The presence and degree of obesity was determined by calculating the body mass index (BMI). [5] Plasma levels of SNA neurotransmitters had been determined by enzyme immunoassay (ELISA) using kits IBL (Germany) - for norepinephrine and Peninsula (UK) - to determine NPY. Blood samples for ELISA had been taken from the cubital vein of the contralateral hand, which measured blood pressure in the morning on an empty stomach, before medication, at rest. At the time of the study, all the examined person had not receive ongoing antihypertensive therapy or it has been canceled 48 hours prior to the inclusion of patients in the study. The plasma was separated by centrifugation and immediately frozen at -70 ° C until analysis. Neuropeptide Y levels had been determined after extraction from plasma using cartridges SEP-COLUMN, containing 200 mg of sorbent C18 (Peninsula). The results are presented as mean and standard error of the mean. Intra-and inter-group differences were evaluated by one-way analysis of variance or χ2-test, depending on the type of data in the program StatPlus Professional (Version 2009 for Windows). A value of P<0.05 was considered statistically significant [2].

Results and discussion.

We obtained that the levels of plasma sympathetic neurotransmitters in the persons surveyed varied considerably depending on the stage of hypertension and BMI (Table 1). Level of noradrenaline in post-stroke hypertensive patients   was greatest in those with a BMI ≥ 35 kg/m2, significantly higher than the same values in patients with a lower body weight.

 

Table 1

Plasma levels of neurotransmitters in the sympathetic depending on the stage of hypertension and body mass index

Index

BMI, kg/m2

≤20

20,1-24,9

25,0-29,9

30-34,99

≥35

1

2

3

4

5

Post-stroke hypertensives (n=50)

Norepinephrine, pg /ml

266,2±3,2

273,2±5,6

269±3,6

278,5±5,2

318,1±4,82

NPY, pg /ml

84,4±2,51

51,3±2,73

45,2±1,8

42,9±4,2

67,8±3,56

Hypertensives free-of-stroke (n=50)

Norepinephrine, pg /ml

248,7±3,5

210±2,63

236,2±6,45

287,3±4,54

291±5,7

NPY, pg /ml

26,2±1,77

16,8±1,1

14,7±0,9

29,7±2,24

38,7±2,72

Control group (n=20)

Norepinephrine, pg /ml

168,3±5,3

110±4,83

175,3±6,15

NA

NA

NPY, pg /ml

12,5±1,4

8,5±1,9

18,1±2,45

NA

NA

Note. 1 - p <0,05 between parameters in group 1, 2-5, 2 - p <0,05 between parameters in subgroup 5 and 1-4, 3 - between the indices in group 2, and 1, 3, 4 - between indicators in group 4, 2.3, 5 - between the indices in group 2, and 3, 6 - p <0,05 between indices in group 5 and 3.4, 7 - p <0,05 between parameters in group 1 and 2, 3.

 

Unexpected results determining the concentration of plasma NPY in the blood of post-stroke hypertensive patients had been revealed. The maximal value of this neuropeptide detected in patients with BMI ≤ 20 kg/m2, significantly higher than the corresponding value in patients with a BMI 20-34,99 kg/m2. In post-stroke hypertensive patients with a BMI ≥ 35 kg/m2 plasma NPY level was 20% (p<0,05) lower compared with patients with BMI ≤ 20 kg/m2. The lowest values of NPY in post-stroke hypertensive patients had been determined in the group with BMI 30-34,99 kg/m2. In patients with non-complicated hypertension plasma content of sympathetic mediators was significantly lower than in patients with previous stroke in anamnesis. The highest level of norepinephrine and NPY was detected in patients with concomitant obesity, second and third degree. The concentration of NPY in patients with BMI ≤ 20 kg/m2 was comparable to the level of the neuropeptide in hypertensive patients with stage II, the first degree of obesity. The lowest values of NPY have been identified in patients with non-complicated essential hypertension and BMI 20,1-29,9 kg/m2.

Normotensive control subjects also had been showed non linear relationship between weight gain and an increase in the concentration of sympathetic neurotransmitters. The lowest concentration of noradrenaline and neuropeptide Y were found in individuals with a BMI 20,1-24,9 kg/m2. An increase in the sympathetic nervous system mediators were found in the group with lower BMI, and in individuals who are overweight.

Obtained results undoubtedly could reflect the important role of the sympathetic nervous system in the pathogenesis of hypertension, as well as in the regulation of metabolic processes. Higher concentrations of norepinephrine and, mainly, NPY had been revealed in post-stroke hypertensive patients, in contrast to patients with non-complicated hypertension. We supposed that it could occur due to impaired secretion of neuropeptide by stroke damaged structures of the central nervous system. Increased concentration of neuropeptide Y in patients with BMI ≤ 20 kg/m2 and mostly unchanged level of norepinephrine might have been the pathogenetic basis to the "obesity paradox", identified in a number of international randomized trials. TEMPiS trial results showed that among 4428 patients with stroke (70% ischemic) the greatest risk of recurrent events and all-cause mortality was found among patients with low body weight, and obesity, however, was associated with a favorable outcoes [9]. Neuropeptide Y is known not only as a sympathetic neurotransmitter, but also as one of the key regulators of metabolism of adipose tissue, increased expression of NPY were found at different stress-associated effects, obesity and anorexia [12]. Increased concentrations of sympathetic neuropeptide Y in patients with BMI ≤ 20 kg/m2 may indirectly reflect hyperadrenergic state and stress levels in group not only hypertensive patients, but also normotensive individuals. Similar trends of neuropeptide Y concentration distributed in groups with non-complicated hypertensive patients and norothensive volunteers had been confirmed the participation of NPY in the regulation of metabolic processes.

Conclusions:

1. Plasma levels of noradrenaline and neuropeptide Y in post-stroke hypertensive patients has been found significantly higher compared with parameters in patients with non-complicated hypertension and normotensive individuals.

2. The concentration of neuropeptide Y has a nonlinear relationship with body mass index in high-risk hypertensive patients normotensive subjects.

3. Plasma level of neuropeptide Y is significantly increased in post-stroke hypertensive patients with BMI ≤ 20 kg/m2 so this fact could explained a pathogenetic substantiation known as "obesity paradox" but it should be analyzed in further studies.

Литература
1. Артериальная гипертония и масса тела. Решенные и нерешенные проблемы / А.Г. Мартынова, А.И. Кодочигова, В.Ф. Киричук, А.А. Ермолаев // Клинич. медицина. - 2005. - Т. 83, № 8. - С. 32-36.
2. Герасимов А.Н. Медицинская статистика / А.Н. Герасимов. - М.: Медицинское информ. агенство, 2007. – 480 с.
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