Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina
For many years, β-blockers have been used to treat patients with coronary heart disease. In patients with stable angina, the effect of β-blockers on the amino acid spectrum of blood serum has been studied. Its violation is considered as one of the pathogenetic links in the development of atheroscl...
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irk-123456789-1805272021-10-02T01:26:11Z Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina Bogdan, T.V. Медицина For many years, β-blockers have been used to treat patients with coronary heart disease. In patients with stable angina, the effect of β-blockers on the amino acid spectrum of blood serum has been studied. Its violation is considered as one of the pathogenetic links in the development of atherosclerosis. The study showed a more efficient action of nebivolol compared to bisoprolol on the amino acid imbalance. In patients with stable angina against the background of antianginal therapy, which included bisoprolol and nebivolol, there was a significant decrease in the total amount of amino acids, the amount of essential amino acids, and the amount of essential amino acids compared to the treatment. Against the background of the nebivolol treatment, there is a positive dynamics of sulfur-containing amino acids (methionine level was maintained, taurine level was significantly increased, cystine level was normalized), isoleucine level was normalized, which indirectly indicates cardioprotective and angiprotective effect of nebivolol. Впродовж багатьох років β-адреноблокатори застосовують для лікування хворих на ішемічну хворобу серця. У хворих на стабільну стенокардію вивчено вплив β-адреноблокаторів на амінокислотний спектр сироватки крові, порушення якого розглядається як одна з патогенетичних ланок розвитку атеросклерозу. Встановлено ефективніший вплив небівололу порівняно з бісопрололом на дисбаланс амінокислот. У хворих на стабільну стенокардію на фоні антиангінальної терапії, що включала бісопролол і небіволол, відмічено достовірне зменшення загальної суми амінокислот, суми замінних амінокислот та суми незамінних амінокислот порівняно з показниками до лікування. На фоні лікування небівололом спастерігалася позитивна динаміка рівня сірковмісних амінокислот (утримався рівень метіоніну, достовірно збільшився рівень таурину, нормалізувався рівень цистеїну), нормалізувався рівень ізолейцину, що опосередковано свідчить про кардіопротекторну та ангіпротекторну дію небівололу. 2021 Article Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina / T.V. Bogdan // Доповіді Національної академії наук України. — 2021. — № 3. — С. 104-108. — Бібліогр.: 8 назв. — англ. 1025-6415 DOI: doi.org/10.15407/dopovidi2021.03.104 http://dspace.nbuv.gov.ua/handle/123456789/180527 616.12-005.4:577.112.3:615.224 en Доповіді НАН України Видавничий дім "Академперіодика" НАН України |
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Медицина Медицина |
| spellingShingle |
Медицина Медицина Bogdan, T.V. Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina Доповіді НАН України |
| description |
For many years, β-blockers have been used to treat patients with coronary heart disease. In patients with stable
angina, the effect of β-blockers on the amino acid spectrum of blood serum has been studied. Its violation is considered
as one of the pathogenetic links in the development of atherosclerosis. The study showed a more efficient action of
nebivolol compared to bisoprolol on the amino acid imbalance. In patients with stable angina against the background
of antianginal therapy, which included bisoprolol and nebivolol, there was a significant decrease in the total amount
of amino acids, the amount of essential amino acids, and the amount of essential amino acids compared to the
treatment. Against the background of the nebivolol treatment, there is a positive dynamics of sulfur-containing amino
acids (methionine level was maintained, taurine level was significantly increased, cystine level was normalized),
isoleucine level was normalized, which indirectly indicates cardioprotective and angiprotective effect of nebivolol. |
| format |
Article |
| author |
Bogdan, T.V. |
| author_facet |
Bogdan, T.V. |
| author_sort |
Bogdan, T.V. |
| title |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| title_short |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| title_full |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| title_fullStr |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| title_full_unstemmed |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| title_sort |
influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina |
| publisher |
Видавничий дім "Академперіодика" НАН України |
| publishDate |
2021 |
| topic_facet |
Медицина |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/180527 |
| citation_txt |
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients with stable angina / T.V. Bogdan // Доповіді Національної академії наук України. — 2021. — № 3. — С. 104-108. — Бібліогр.: 8 назв. — англ. |
| series |
Доповіді НАН України |
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AT bogdantv influenceofbisoprololandnebivololonthespectrumofsubstitutedaminoacidsinbloodplasmaofpatientswithstableangina |
| first_indexed |
2025-07-15T20:38:37Z |
| last_indexed |
2025-07-15T20:38:37Z |
| _version_ |
1837746800126066688 |
| fulltext |
104
ОПОВІДІ
НАЦІОНАЛЬНОЇ
АКАДЕМІЇ НАУК
УКРАЇНИ
ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2021. № 3: 104—108
Ц и т у в а н н я: Bogdan T.V. Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in
blood plasma of patients with stable angina. Допов. Нац. акад. наук Укр. 2021. № 3. С. 104—108. https://doi.
org/10.15407/dopovidi2021.03.104
β-blockers remain the basic drugs for the treatment of coronary heart disease (CHD). For many
years, they have been used to treat patients with stable angina (SA), unstable angina (UA), and
myocardial infarction (MI). The mechanism of antianginal action of these drugs is associated with
a decrease in heart rate, myocardial contractility and a decrease in systolic blood pressure. The
increase in the coronary blood flow is explained by the prolongation of the period of diastolic
filling of the ventricles of heart and the decrease in vasoconstriction of the coronary arteries
during exercise. β-blockers are recognized as antianginal drugs of the first choice. However, for-
mally, there is no evidence of their beneficial effect on the survival of patients with SA. The prog-
nostic effect of β-blockers has been proven only in patients who have suffered from MI or UA, i.e.,
in the implementation of secondary prevention of acute coronary syndrome. One of the reasons
for extrapolating these data to the recommendations for primary prevention was the proven
https://doi.org/10.15407/dopovidi2021.03.104
UDC 616.12-005.4:577.112.3:615.224
T.V. Bogdan, https://orcid.org/0000-0002-6441-1410
Bogomolets National Medical University, Kyiv
E-mail: taviza@mail.ua
Influence of bisoprolol and nebivolol
on the spectrum of substituted amino acids
in blood plasma of patients with stable angina
Presented by Academician of the NAS of Ukraine V.P. Shyrobokov
For many years, -blockers have been used to treat patients with coronary heart disease. In patients with stable
angina, the effect of -blockers on the amino acid spectrum of blood serum has been studied. Its violation is considered
as one of the pathogenetic links in the development of atherosclerosis. The study showed a more efficient action of
nebivolol compared to bisoprolol on the amino acid imbalance. In patients with stable angina against the background
of antianginal therapy, which included bisoprolol and nebivolol, there was a significant decrease in the total amount
of amino acids, the amount of essential amino acids, and the amount of essential amino acids compared to the
treatment. Against the background of the nebivolol treatment, there is a positive dynamics of sulfur-containing amino
acids (methionine level was maintained, taurine level was significantly increased, cystine level was normalized),
isoleucine level was normalized, which indirectly indicates cardioprotective and angiprotective effect of nebivolol.
Keywords: -blockers, bisoprolol, nebivolol, amino acids.
МЕДИЦИНА
MEDICINE
105ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2021. № 3
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients...
ability of β-blockers to reduce the number of episodes of painless myocardial ischemia, according
to Holter ECG monitoring [1, 2].
In addition to the already known mechanisms of action of β-blockers, it is worth noting
the property of nebivolol to promote the release of nitric oxide (NO), which is one of the most
important mediators functionally involved in various biological processes [3—6].
In previous studies, we obtained data on the violation of the amino acid spectrum of blood
plasma in patients with emergencies [7, 8]. It is advisable to study the effect of bisoprolol and
nebivolol on the spectrum of plasma amino acids in patients with SA.
We examined 75 patients with emergencies aged 65 to 76 years (mean age of patients —
68.2 years ± 6.3 years). Patients were divided into two groups: I — 37 persons who received
cardiket, bisoprolol, atoris, enap, acetylsalicylic acid, clopidogrel; II — 38 persons whose therapy,
in addition to these drugs, included L-arginine (100 ml intravenously for 10 days). All groups of
patients were statistically homogeneous and comparable. The study did not include patients
with heart failure stage IIB and III, atrial fibrillation, comorbidities in the stage of decompen-
sation, cancer, and diseases of the musculoskeletal system.
Serum amino acids (AA) were used as the object of the study. The method of ion exchange
liquid column chromatography was used. The following AA substitutes were determined in blood
serum: ornithine, taurine, aspartic acid, serine, glutamic acid, proline, glycine, alanine, cysteine,
tyrosine, and glutamine. The results of the research were processed on a personal computer using
the Microsoft Office software package. For the statistical processing of the obtained data, Microsoft
Excel 2010 was used. The significance of the difference between the average values of the indica-
tors of different groups was determined by the definition of Student’s t-test or Pearson’s test.
73 patients aged 58 to 75 years (mean age — 67.2 years ± 5.2 years) with SA were divided
into two groups: During the day in basic therapy, group I (38 patients) received bisoprolol, ena-
lapril, atorvastatin, acetylsalicylic acid, and isosorbide dinitrate, group II (35 patients) received
nebivolol, enalapril, rosuvastatin, acetylsalicylic acid, and isosorbide dinitrate. Examination of
patients was performed at the beginning of the treatment and after 20 days. The control group
(CG) included 18 healthy people aged 49—58 years (mean age — 53.4 years ± 4.7 years). In pa-
tients taking nebivolol, compared with patients treated with bisoprolol, the level of total AA in-
creased significantly by 31.29 μmol/100 ml, the amount of nonessential AA — by 22.22 μmol/100 ml,
the amount of irreplaceable AA — by 9.13 μmol/100 ml, although, in both groups of patients,
these indicators remained significantly lower compared to CG. It should be noted that against
the background of therapy with nebivolol did not change the level of AA with a branched
side chain compared to pre-treatment, and with bisoprolol the amount of these AA decreased
even more compared to CG by 31.99 μmol/100 ml and with an indicator before treatment — by
9.66 μmol/100 ml (Table 1).
The analysis of the results showed that, against the background of treatment in patients of
both groups, there was a significant decrease in arginine levels compared to pre-treatment —
by 4.18 and 1.97 μmol/100 ml. Compared with CG, the level of AA in patients receiving bisopro-
lol decreased by 6.03 μmol/100 ml, and in patients receiving nebivolol — by 3.82 μmol/100 ml
(Table 2).
It is noteworthy that in patients of the two studied groups against the background of treat-
ment significantly decreased the level of ornithine in plasma compared with pre-treatment —
106 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2021. № 3
T.V. Bogdan
by 2.48 and 1.23 μmol/100 ml. Compared with CG in patients receiving nebivolol, ornithine
levels returned to normal. It should be noted that, in patients with SA whose therapy included
nebivolol, significantly increased the level of taurine in plasma compared with pre-treatment by
2.78 μmol/100 ml, while in patients whose therapy included bisoprolol, the level of this AA did
not change significantly.
After treatment, patients receiving nebivolol, in contrast to patients receiving bisoprolol, signi-
ficantly increased the plasma serine levels by 3.0 μmol/100 ml, glutamic acid — by 2.49 μmol/100 ml.
Significantly, in patients with SA receiving bisoprolol and nebivolol, the level of cysteine in the
blood plasma was significantly reduced compared to treatment — by 3.4 and 3.2 μmol/100 ml. But
in patients receiving nebivolol, the level of this AA compared with CG was normalized.
Table 1. The effect of bisoprolol and nebivolol on the amino acid spectrum
of blood plasma in patients with SA, μmol/100 ml (M ± m)
Indicator CG (n 8)
Before treatment
(n 73)
On treatment
Bisoprolol
(n 38)
Nebivolol
(n 35)
General amount of AA 352.45 ± 10.40 236.6 ± 6.7 172.11 ± 7.50*#& 203.4 ± 5.3*#
Nonessential АA 275.96 ± 8.80 152.62 ± 6.50 110.04 ± 5.60*#& 132.26 ± 5.80*#
Sulfur-containing АA 19.43 ± 2.10 14.37 ± 0.90 10.44 ± 1.20*# 13.19 ± 1.30*
АA with a branched chain 50.62 ± 3.50 28.28 ± 1.60 18.63 ±1.50*#& 24.33 ± 2.30*
*Significant difference in relation to the control group. #Significant difference in terms of indicators for treat-
ment. &A significant difference between groups of patients.
Table 2. The effect of bisoprolol and nebivolol on the spectrum of replacement
amino acids in the blood plasma of patients with SA, μmol/100 ml (M ± m)
Indicator CG (n 18)
Before treatment
(n 73)
On treatment
Bisoprolol
(n 38)
Nebivolol
(n 35)
Ornithine 14.36 ± 1.20 15.09 ± 1.10 12.61 ± 1.30* 13.86 ± 1.10#
Taurine 9.02 ± 0.44 3.44 ± 0.06 3.88 ± 0.07# 6.22 ± 0.09*#&
Aspartic acid 2.12 ± 0.06 2.79 ± 0.05 2.61 ± 0.05 2.84 ± 0.07
Serin 18.75 ± 1.43 11.5 ± 0.9 11.89 ± 0.60# 14.5 ± 0.5*#&
Glutamic acid 22.64 ± 1.16 12.25 ± 0.08 13.53 ± 0.70# 14.74 ± 0.60*#
Proline 21.42 ± 1.27 10.94 ± 0.09 9.11 ± 0.75# 10.67 ± 0.64*
Glycine 31.84 ± 2.24 26.58 ± 0.70 20.48 ± 1.55*# 21.65 ± 0.43*#
Alanine 46.53 ± 1.31 42.78 ± 1.30 31.01 ± 1.24*# 32.13 ± 1.33*#
Cysteine 6.82 ± 0.31 8.32 ± 0.06 4.92 ± 0.05* 5.12 ± 0.06#
Tyrosine 6.32 ± 0.08 6.72 ± 0.07 4.35 ± 0.09*# 5.67 ± 0.09#&
Glutamine 51.89 ± 2.45 12.21 ± 0.70 4.58 ± 0.05*# 4.86 ± 0.05#
*Significant difference in relation to the control group. #Significant difference in terms of indicators for treat-
ment. &A significant difference between groups of patients.
107ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2021. № 3
Influence of bisoprolol and nebivolol on the spectrum of substituted amino acids in blood plasma of patients...
The level of tyrosine in patients receiving bisoprolol was significantly reduced compared
with CG by 1.97 μmol/100 ml, and with the pre-treatment index by 2.37 μmol/100 ml. In patients
treated with nebivolol, the tyrosine levels did not change significantly from CG and pre-treat-
ment. Significantly, patients in both groups significantly decreased plasma ammonia levels after
treatment — by 6.37 and 15.77 μmol/100 ml, respectively. Against the background of nebivolom
treatment revealed a more significant decrease in plasma ammonia, which, of course, is a posi-
tive factor in this category of patients.
Conclusions.
1. In patients with SS against the background of antianginal therapy, which included bisop-
rolol and nebivolol, there was a significant decrease in the total amount of AA, the amount of
nonessential AA and the amount of essential AA compared with pre-treatment and CG, however,
in patients receiving nebivolol, the catabolism occurs slower, as evidenced by a significant dif-
ference between these indicators between the two groups of patients after treatment.
2. Against the background of nebivolol treatment, there is a positive dynamics of sulfur-con-
taining AA levels: methionine levels were maintained, taurine levels were significantly increased,
and cystine levels were normalized, which indirectly indicates the cardioprotective and antipro-
tective effects of nebivolol.
3. Against the background of antianginal therapy with nebivolol, there is significantly less
use of arginine than in patients receiving bisoporolol, which indicates the activation of compen-
sation processes.
4. Nebivolol normalized the level of isoleucine, which is a part of the tricarboxylic acid cycle
and promotes mitochondrial biogenesis in myocardium and other muscles, preventing the oxi-
dative stress.
5. In patients with SA receiving antianginal therapy with the inclusion of nebivolol, against
the background of the normalization of ornithine, a significant decrease in the ammonia levels was
observed compared with those in patients receiving bisoprolol.
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Received 01.01.2021
Т.В. Богдан, https://orcid.org/0000-0002-6441-1410
Національний медичний університет ім. О.О. Богомольця, Київ
E-mail: taviza@mail.ua
ВПЛИВ БІСОПРОЛОЛУ ТА НЕБІВОЛОЛУ
НА СПЕКТР ЗАМІННИХ АМІНОКИСЛОТ ПЛАЗМИ КРОВІ
У ХВОРИХ НА СТАБІЛЬНУ СТЕНОКАРДІЮ
Впродовж багатьох років β-адреноблокатори застосовують для лікування хворих на ішемічну хворобу
серця. У хворих на стабільну стенокардію вивчено вплив β-адреноблокаторів на амінокислотний спектр
сироватки крові, порушення якого розглядається як одна з патогенетичних ланок розвитку атеросклерозу.
Встановлено ефективніший вплив небівололу порівняно з бісопрололом на дисбаланс амінокислот. У хво-
рих на стабільну стенокардію на фоні антиангінальної терапії, що включала бісопролол і небіволол, від-
мічено достовірне зменшення загальної суми амінокислот, суми замінних амінокислот та суми незамінних
амінокислот порівняно з показниками до лікування. На фоні лікування небівололом спастерігалася по-
зитивна динаміка рівня сірковмісних амінокислот (утримався рівень метіоніну, достовірно збільшився
рівень таурину, нормалізувався рівень цистеїну), нормалізувався рівень ізолейцину, що опосередковано
свідчить про кардіопротекторну та ангіпротекторну дію небівололу.
Ключові слова: β-адреноблокатори, бісопролол, небіволол, амінокислоти.
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