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Deutscher Wissenschaftsherold • German Science Herald, N 1/2021
ISSN 2509-4327 (print)
ISSN 2510-4780 (online)
Deutscher Wissenschaftsherold
German Science Herald
№ 1/2021
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© Deutscher Wissenschaftsherold – German Science HeraldDeutscher Wissenschaftsherold • German Science Herald, N 1/2021
DDC-UDC 616.12-008.331.1-06:616.127-07 DOI:10.19221/202114
Khrebtii H.I.,
PhD, Associate Professor of Internal Medicine, Physical Rehabilitation and Sports Medicine,
Higher Education Institution in Ukraine ”Bukovinian State Medical University”, Teatralnaya Square2,Chernivtsi, Ukraine,
58002, galinahrebtiy@gmail.com
Kotsiubynska K.M.,
Sokoliuk V.B.,
Stetsyk N.I.,
Malyshevska I.V.
Cardiologist of Chernivtsi Regional Clinical Cardiology Center
ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE
Abstract. The research conducted allowed us to set the pecularities of vascular motor function of the
vessels, carbohydrate and lipid metabolism of the patients with arterial hypertension and insulin
resistance, and also new possibilities of medical correction of the detected dysfunctions. The
effectiveness of the new treatment scheme of the patients with arterial hypertension accompanied by
insulin resistance by adding to the treatmen L-arginine- the predecessor of nitric oxide has been
examined in this work. The average duration of the research was 3 months. Including a conditionally
essential amino acid L-arginine to a combined antihypertensive therapy with the help of lisinopil and
amplodipine and to hypolipidemic therapy with atorvastatin had significant benefits in increasing
endothelium dependent vasodilatation, decreasing HOMA-index and also in more effective correction
of hypertriglyceridemia.
Key words: arterial hypertension, insulin resistance, L- arginine, endothelial dysfunction, lipid
metabolism.
Introduction. Cardiovascular diseases (CVD) - IR-is an insufficient biological responce of the
hold one of the leading places in the causes of cells to insulin action with its sufficient
death in Ukraine [1]. Decisive role in increasing of concentration in blood [8]. Causal connection of
cardiovascular pathology is being played by the endothelial dysfunction (ED) and IR still are
negative ”acqusions” of the modern society - disputable. In numerous researches it has been
sedentary lifestyle, chronic stress and increasing demonstrated that ED is the consequence of those
of caloric value of the food. Those modifying risk mechanisms, that lie in the basis of IR -
factors lead to incessant increasing to arterial hypeglycemia, arterial hypertension (AH) and
hypertension (AH),dyslipidemia, adiposity and dyslipidemia. With hyperglycemia a protein
insulin resistance [2, 3]. kinase-C enzyme is being activated in endothelial
Nowadays AH is considered as a endothelium cells, that increases vascular cells permeability for
dysfunction (ED) condition, that is accompanied proteins and breaches endothelium dependent
by constriction of vascular smooth muscles, vasodilatattion (EDV) [9]. Besides this,
increasing of left ventricle emission resistance and hyperglycemia activates the processes of lipid
predisposition to atherosclerosis [3, 4]. pereoxidation, which products inhibit
Endothelial dysfunction of the vessels is vasodilatory function of endothelium. With AH, a
pathogenetically connected with insulin defection of endothelial cells architectonics,
resistance (IR) development, that is observed in a increase production of vasoconstrictor
significant number of patients with AH and lies in endothelin-1, vascular remodelling with
the basis of metabolic syndrom [5, 6]. The hardening of blood vessels takes place. Thus, the
accumulated experimental and clinical material mechanisms mentioned above reduce EDV while
together with epidemiological researches, that increasing the permeability of endothelium and
showed increase of insulin level in patients with adhesion molecules expression [10]. Other
AH, certainly indicate that IR is an important researchers consider that ED leads to IR
pathogenetical link of AH [7]. development in the consequence of defection of
© 2019. This manuscript version is made available under the CC BY-NC 4.0 license 15
Anzeige – Info@dwherold.de http://creativecommons.org/licenses/by-nc/4.0/Deutscher Wissenschaftsherold • German Science Herald, N 1/2021
transendothelial transportation of insulin [11]. Endothelium dependent vasodilatation (EDV)
With no doubt, IR and ED , including production has been determined with the help of D.
of NO, are closely connected with each other and Celemajer test. The evaluation of flow induced
build a pathological ”vicious circle”, that leads to vasodilatation has been held by means of
metabolic and cardiovascular diseases. Despite measuring artery diameter in the phase of
the fact that a lot of causal connections in reactive hyperemia (after vascular
pathogenesis of ED are still not found out , it is an decompression). EDV was defined as a ratio of
unconditional fact, that ED is the first link in changes in the value of the diameter of brachial
atherosclerosis development, that is connected artery after tests held with reactive hyperemia to
with IR syndrom. its value in the tranquility state. A normal reaction
In this direction, in our opinion, it is perspective of brachial artery has been considered to be its
to study the influence of natural predecessor NO- dilatation on the background of test with reactive
L-arginine on the functional condition of vascular hyperemia more than 10% from its original value.
endothelium, and also on carbohydrate and lipid Dilatation of less than 10% witnessed of violations
metabolism of the patients with hypertonic of EDV. A test with peropherialvasodilator
disease accompanied by insulin resistance. nitroglycerin was held after the patient had spend
L-arginine (α-amino-δ-huanido valerian acid) - 15 minutes in the state of tranquility. Endothelium
conditionally essential acid, that is an active and not dependant vasodilatation (ENDV) was
versatile cell regulator of numerous vital body calculated as a ratio of the artery diameter change
functions. L-arginine is a substarate for NO- after taking nitroglycerin to its original (initial)
synthase-enzyme, that catalyzes synthesis of NO value. A normal reaction of brachial artery has
in endothelials [12]. been considered to be its dilatation to more than
Material and research methods. For the basis 20%. In all observation groups, we have also
of this reserach, the examination results of 37 measured the speed of bloodflow in the brachial
patients with AH II stage, chronic heart failure artery in the state of tranquility and on the
(CHF) 0-I stage, I-II functional classes (FC), aged background of test with hyperemia (V, m/s). The
from 60-88 years old (the average age was ratio of change of the blood flow speed in the
(77,3+0,8 years) and concomitant insulin brachial artery after the test with reactive
resistance were taken. All the patients were hyperemia to its value in the state of tranquility
males. was also determined.
Criteria for exclusion from the research: According to the scheduled design of research,
symptomatic arterial hypertensions, clinical and all the patients with AH of II stage received
electrocardiographic symptoms of CHD, combined antihypertensive therapy with an
dysfunctions of sinoartrial and atrioventricular inhibitor of angiotensin converting enzyme
conductance of II-III stage, auricle fibrillation, lisinopril in the dosage of 5-20 mg/day,
frequent ventricular and supraventricular beats, hypolipidemic therapy with atorvastatin in the
AH of I and III stages, abdominal adiposity of II and dosage of 10 mg per day. While examining
III stages, CHF of II-III stages, III-IV FC, glucose level prescribed doses of antihypertensive medication,
in blood plasma fasting ≥ 6,1 mmol/l, diabetes, that were used to reach the target levels of BP, in
chronic obstructive lungs diseases, chronic most cases the usage of lisinopril in the dosage of
diseases of alimentary canal and kidneys in the 10 mg per day and amlodipine in the dosage of 5
acute phase, endocrinological diseases. mg per day took place. The average dosage of
To diagnose insulin resistance HOMA-index lisinopril in the patients with AH of II stage was
(Homeostasis model assessment) has been used, (12,3 + 0,8) mg,the average dose of amlodipine
that has been calculated according to the formula: (6,1 + 0,3) mg.
HOMA = insulin level in blood fasting (mIU/ml) Among the patients with AH, a group of
multiplied by glucose level in blood fasting patients (19 people) was separated, that besides
(mmol/l) and divided by 22,5. A normal index has the above mentioned treatment scheme,
been considered HOMA-index not greater than additionally received infusive and oral L-arginine
2,77 [13]. forms. In the period of 12-14 days (the period of
16Deutscher Wissenschaftsherold • German Science Herald, N 1/2021
hospital stay), the patients were daily infused with different therapy schemes after 3 months of
100 ml of Tivortin solution (4,2% solution of L- observation. In 3 months, EDV in the selected
arginine chloride). After checking out of the groups of the patients under the effect of basic
hospital, the patients orally took 40 minutes therapy scheme increased by 63,1%, and with
before the meal 20 ml of Tivortin aspartat solution additional prescription of L-arginine to 97, 9%.
(4 gramms of L-arginine)(4 measuring spoons) Increase, induced by the blood flow of EDV,
twice a day. The treatment course of infusive and while taking 6gr per day of L-arginine was
oral forms – 3 months (90 days). The evaluation of confirmed by J.P. Lekakis et al. [18] in prospective
effectiveness was held after 3 months from the randomized double blind study with the
beginning of the prescribed treatment. participation of 35 patients with AH. Taking L-
Static processing of the research results was arginine significantly increased dilatation of
conducted with the help of variation statistics brachial artery, due to blood flow (1,7+3,4%
mehtods, using the programmme StatSoft compared to з 5,9+5,4%; d = 0,008). In a research,
”Statistica” v. 6.0. The majority of the indicators held by A. Palloshi et al., oral intake of L-arginine
bore abnormal distribution (the distribution type 6gr per day by the patients with microvascular
was determined with the help of Shapiro-Wilks stenocardia and AH, significantly increased EDV
test), that’s why we used the methods of non- and the level of cyclic GMP [19].
parametric statistics. The research results were The changes in the basic parameters of
represented as median and interquartile swing carbohydrate metabolism under the influence of
(25-75 percentiles). The differnce of рDeutscher Wissenschaftsherold • German Science Herald, N 1/2021
Table 1
The dynamics of endothelial functions of the vessels of the patients with hypertonic disease with
insulin resistance under the influence of different treatment schemes
Basic therapy+L-
Basic therapy Result after 3
Indicators arginine
(n=18) months
(n=19)
EDV, %
Original value -3,5 (-7,4; 3,8) -4,4 (-7,5; 4,8)
After 3 months 3,7 (0; 9,9) 5,4 (4,4; 7,7)
Dynamics, % 63,1 (-13,1; 108,0) 97,9 (68,9; 202,8) 0,036
d-(o-3)Deutscher Wissenschaftsherold • German Science Herald, N 1/2021
Table 2
Dynamics of carbohydrate metabolism parameters of the patients with hypertonic disease with
insulin resistance under the influence of different treatment schemes
Basic therapy+
Biochemical Basic therapy
L-arginine р
parameters (n=18)
(n=19)
Glucose mmol/l
Original value 4,95 (4,55; 5,75) 5,10 (4,60; 5,40)
After 3 months 5,00 (4,60; 5,45) 4,90 (4,60; 5,50) After 3months
Dynamics, % 2,0 (-5,6; 4,9) -2,1 (-5,2; 3,1) 0,87
Insulin мОД/ml,
Original value 11,45 (10,75; 12,20) 11,40 (10,60; 12,20)
After 3 months 11,20 (10,50; 11,70) 11,00 (10,20; 11,90) After 3 months
Dynamics, % -3,2 (-10,2; 1,2) -3,7 (-14,5; 2,5) 0,78
НОМА
Original value 2,79 (2,77; 2,88) 2,80 (2,78; 2,86)
After 3 months 2,71 (2,53; 2,82) 2,63 (2,52; 2,77)* After 3 months
Dynamics, % -4,1 (-9,6; 2,4) -6,1 (-13,8; -0,3) 0,26
Notes:
1. Symbol: НОМА (Homeostasis model assessment) – index, that is used for determination of insulin
resistance.
2. *Deutscher Wissenschaftsherold • German Science Herald, N 1/2021
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