To date, most authors agree that the gestational
hypertension, as a component of preeclampsia is associated with endothelial dysfunction,
arises in pregnancy pathology.
The purpose of the study of endothelium-dependent vasodilation (EDVD) of the brachial artery,
endotelin 1.2 in plasma and stable metabolites
Nitric oxide (NO) in the urine of women with normally proceeding pregnancies and
pregnancy complicated by different clinical variants of preeclampsia and evaluation
effectiveness of the influence of amlodipine (normodipin) on parameters of blood pressure and EDVD.
Materials and methods
primigravidas women aged 18 to 32 years (mean
age 26,1 ± 1,7 years), in terms of pregnancy weeks of 3439, divided into three
group. 1yu (main) group consisted of 23 women during pregnancy
complicated by the development of nephropathy III degree from a leading syndrome
arterial hypertension. The average value of systolic blood pressure (SBP) in patients
this group was 156,8 ± 4,7 mm Hg, diastolic (DBP) 95,9 ± 2,1 mm Hg. From
patients of the first group of 11 women as antihypertensive therapy received
amlodipine (normodipin "Gedeon Richter), single dose of 5 mg / day for 3
weeks. In 2u group (16 persons) were included women who have preeclampsia
revealed only swelling I and II degree. In this group, SBP was 118,5 ± 3,1
mm Hg, DBP 75,2 ± 1,1 mm Hg In the third (control) group included 20 women with
physiological pregnancy. GARDEN they were 115,7 ± 3,8 mm Hg, DBP
73,8 ± 1,7 mm Hg In addition, as another control group
studied 12 healthy nonpregnant women (NSA) of the appropriate age.
Condition EDVD brachial artery was assessed using a linear transducer 7.5 MHz
ultrasonic system "Simens Sonoline 1700". The study was conducted in
triplex mode. Brachial artery diameter and blood velocity was measured in her
before and after 5minutnoy occlusion (reactive hyperemia). Calculate the percentage
growth of these parameters after occlusion. The content of endothelin 1,2 (ET1, 2)
in plasma was determined by radioimmunoassay using commercial kits firms "Amersham"
(England). NOsistemy activity was assessed by the total urinary excretion
stable metabolites NOnitratov and nitrites. Nitrate reduction to
nitrite in urine was performed in reaktorevosstanovitele "Nitrate reduktor" (Firm
"World Preciston Instasments, Inc.", USA). The color intensity was measured
spectrophotometrically at a wavelength of 540 nm. The calibration curve
The concentration of nitrite. The total excretion of stable NO metabolites
calculated on the volume of daily urine. The results obtained are statistically
processed using software package "Statistica".
Significant changes during treatment were assessed using paired test
Student.
Results and discussion
Study indicators EDVD pregnant women of different groups revealed the following (Table
1). In the control group NSA source artery diameter was significantly smaller than
pregnant women of all three groups. Apparently, the larger diameter of the artery at
pregnancy due to increased content in the blood of these women, estrogen
which are known to have vasodilatory effects. Similar
changes concerned the initial velocity of blood flow in the arteries. Within 15 seconds after
cessation of occlusion of the NSA, the authentic, almost 30% increase
the diameter of the artery andmorethan twice the rate of increased blood flow. Y
healthy pregnant women (third group) reactive hyperemia also led to
significant increase in brachial artery diameter and increase in the rate
blood in it compared to the initial state. It should be noted that
percentage increase in vessel diameter and blood flow velocity in it for women Group 3
compared with the NSA was somewhat lower, although the absolute values of these
indices were significantly higher.
Patients in group 2 with edema pregnant and normal values of blood pressure
reaction of the brachial artery to reactive hyperemia was similar to that
was observed among women in group 3.
However, in pregnant 1st (main) group with nephropathy and the presence of
hypertension was observed paradoxical reaction of brachial artery in
response to reactive hyperemia. Within 15 seconds after the cessation of occlusion they do not
vasodilatation occurred, and there is a further spasm of the artery. Noted
reducing the diameter of the vessel by an average of 9% of the initial value. Increase
blood flow, they had almost two times less than in pregnant third
group and 1.5 times than the 2nd.
Determination of ET1, 2 in the plasma showed (Table 2) that the average
levels of the peptide in women 2nd and 3rd groups was approximately the same inmorethan
two times less than in the control (NSA). However, in pregnant 1st group, in contrast
from the previous two, its content was significantly higher, although not different
from the control.
However, the content of NO metabolites in the urine of healthy pregnant women (3rd
group) is almost three times higher than in controls. Women with
Nephropathy and edema (group 2) showed a significant reduction in their comparison
a third group of pregnant women. However, the lowest content of stable metabolites
NO observed in pregnant women with nephropathy leading syndrome of hypertension. Contents
nitrate / nitrite in the urine of these was significantly lower than that of two pregnant
other groups.
for correction of high blood pressure, 11 women, in terms of pregnancy 36 weeks and above,
taking amlodipine (normodipin). Is set sufficiently high efficiency
dasg, since after 2448 hours of initiation of the normalization
BP in 9 of 11 pregnant women. By stage of labor in all subjects was observed in BP
within the physiological norm. SAD at this time averaged
119,2 ± 4,7 mm Hg, DBP 74,1 ± 1,3 mm Hg (P <0,01). Along with the clinical
effectiveness of women in this group was observed and recovery vasoregulating
vascular endothelial function (Table 3). After the test with "reactive hyperemia"
in all cases there is an increase in brachial artery diameter. Average
magnitude increase in diameter was 7,43 ± 1,48% (p <0,05), blood flow velocity
60,57 ± 6,94% (p <0,05). However, it should be noted that these figures were
somewhat lower than in healthy pregnant women.
Currently, most researchers consider preeclampsia and its
Various clinical manifestations in terms of systemic endothelial
dysfunction. Established that the endothelium has a unique
ability to respond to various humoral changes in the environment
production of vasoconstrictor and vasodilator factors, the balance of which
determines the tone of smooth muscle cells and is important in the regulation of blood pressure
. Proved that hypertension is accompanied by a breach EDVD
. Our data showed that both gestational
hypertension was also observed in endothelial dysfunction. Perhaps the lack of
adequate response of brachial artery in pregnant women with hypertension was associated with the presence of
these imbalances in the major vasoregulating systems - endothelin - nitric oxide.
Definite confirmation of this could serve as a low level of stable
NO metabolites in the urine, indicating a deficiency of nitric oxide, and increased
content of ET-1, 2 women in Group 1 with gestational hypertension, in contrast to
patients of the other two groups. Previously, several authors have also noted similar
changes in the content of ET-1 in hypertensive pregnancy and preeclampsia. More
addition, some researchers believe that increased levels of ET-1 in
pregnant women with hypertension, along with hypeasricemia may serve as a marker of severity
preeclampsia. It should be noted that in our observations the level of ET-1, 2 in healthy
pregnant women as well as in women with edema, but normal blood pressure, was almost two
times lower than in controls. We believe that in this case the reduction of
ET-1, 2 in plasma is a physiological adaptation process. Established
that low concentrations of ET-1 via activation of receptors such as ET-B, leads to
release of endothelial vasodilating factors, thereby
vasodilation. Similar adaptations have noted some
The authors and the content of other endogenous chemical regulators. This, in
turn, could help to reduce systemic vascular
resistance observed in pregnant women with normotension. Same
physiological adaptation processes can be considered, and elevated levels of
NO metabolites in healthy pregnant women and patients in group 2 compared with
control. However, we have established an increase in the content of ET-1, 2 and
reduction of NO metabolites in women with gestational hypertension (compared with
the other two groups) is not only an indication that they have the
endothelial dysfunction, but also to some extent, could lead to
the emergence of a paradoxical response of brachial artery occlusion. It is known that
in contrast to the low-dose subporogovye concentration ET-1 by acting on receptors
ET-A, cause vasoconstriction and increase the sensitivity of vascular smooth muscle
to catecholamines. In our view, this concentration of ET-1, 2 y
pregnant women with hypertension had subporogovuyu value with respect to healthy pregnant women.
Thus revealing an imbalance leading vasoregulatory systems could be
one of the mechanisms of formation of pregnant women with hypertension, hypertensive hypodynamic
dissociation. It was for her characteristic combination of high peripheral
vascular resistance with low cardiac output. This type of
hemodynamic disorders most frequently observed in gestational
Hypertension. It is important to note that timely and adequate
antihypertensive therapy for gestational hypertension - the most realistic
way of preventing perinatal complications in mother and newborn. In
present during antihypertensive therapy preference is given to
dasgs, allowing not only to effectively control blood pressure, but also affect
major pathogenetic links in the formation of hypertension, providing
organo action. However, only a relatively small number of
simple and well-tolerated antihypertensive dasgs approved for use in
pregnancy, and amlodipine (normodipin) among them.
Conclusions
1. For physiological pregnancy is characterized by the balance of the main vasoactive
factors of endothelial origin, namely the low level of ET1, 2 in the plasma and
high content of stable NO metabolites in daily urine, which contributes
maintaining an adequate response of brachial artery in response to "shear stress".
2. In pregnant women with preeclampsia infringement EDVD brachial artery, which
depends on the shape of preeclampsia. When pregnant edema observed inadequate
reaction of the artery in response to short-term occlusion, and nephropathy in pregnant women
with the symptom of hypertension is a paradoxical response in the form
spasm, accompanied by a twofold decrease in blood flow velocity.
3. In pregnant women with gestational hypertension violation EDVD combined with
high content in their blood plasma ET1, 2, along with low
stable NO metabolites in plasma and urine daily.
4. Amlodipine (normodipin) with gestational hypertension
helps to normalize blood pressure and restore EDVD.
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Published with permission from Russian
Medical Journal .