The Role of Plasma Endothelin-1 in Preeclampsia

Tr. J. of Medical Sciences
29 (1999) 21–24
© TÜBİTAK
Yalçın KİMYA1
The Role of Plasma Endothelin-1 in Preeclampsia
Candan CENGİZ1
Hakan OZAN1
Levent BÜYÜKUYSAL2
Sami AYDIN2
Serhat TATLIKAZAN1
Received: January 24, 1997
Abstract: Endothelin-1 levels in normal and
thrombocyte and white blood cell counts,
preeclamptic pregnant women were
proteinuria, systolic and diastolic blood
determined serially to investigate the
pressures. There was no significant
correlation between renal function tests and
difference between the mean plasma
the severity markers of preeclampsia.
endothelin-1 concentrations of the
preeclamptic and uncomplicated groups at all
Plasma endothelin-1 levels were determined
gestational weeks but at the time of delivery.
in 45 serial plasma samples from 15
None of the endothelin-1 values at any
pregnant women who subsequently
gestational week differed significantly from
developed preeclampsia, and in 43 plasma
any other in the study group; therefore, the
samples from 25 women with uncomplicated
risk of subsequent development of
pregnancies retrospectively. Renal function
preeclampsia could not be estimated by
tests, complete blood counts, urinalysis and
plasma endothelin-1 measurements.
blood pressure measurements were
performed during antenatal follow-ups of
these patients.
Key Words:
Endothelin-1, pregnancy,
Departments of 1Obstetrics and Gynecology.
2Pharmacology, Medical Faculty, Uludağ
No correlations were set between plasma
preeclampsia.
University, Bursa-Turkey.
endothelin-1 levels and renal function tests,
Introduction
At the time of joining the study and just before
A factor in circulation may lead to endothelial cell
delivery all women had blood samples taken for
damage and contribute to the development of
determination of endothelin, urea, uric acid, creatinine
preeclampsia (1, 2). Plasma endothelin–1 (ET–1), which
and complete blood counts. Proteinuria was also
is liberated by the endothelial cells, is the most potent
determined by the ESBACH method. Each patient was
endogenous vasoconstrictor known, and its efficacy has
physically examined and blood pressure was recorded at
been shown to be potentiated in arteries without
the initial visit. During monthly follow–ups, in addition to
endothelium (3, 4). To determine the importance of ET–1
blood pressure determinations, peripheral blood samples
in the pathophysiology of preeclampsia, we studied the
were taken for ET–1 measurements.
levels of ET–1 in normal and preeclamptic pregnant
Blood samples for ET–1 were collected into prechilled
women serially and investigated the correlation between
test tubes containing aprotinin at a concentration of 400
the renal function tests and the severity markers of
kallikrein inhibitor units per milliliter and disodium
preeclampsia.
ethylenediaminetetraacetic acid at a concentration of 1.5
mg/ml for 5 milliliters of blood. All samples were
immediately centrifuged at 3000 rpm for 10 minutes and
Materials and Methods
the plasma was then removed and stored in vacutainer
This study included 437 pregnant women and was
tubes at –70°C until assay, for a maximum of 22 months.
conducted between January 1993 and August 1995. The
Patients were classified as preeclamptic if they fulfilled
study was approved by the ethical committee and the
the standard criteria: absence of a history of hypertension
participants signed a written consent form.
before pregnancy and confirmation by anamnesis with
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The Role of Plasma Endothelin-1 in Preeclampsia
fundoscopic examination, blood pressure higher than
However, the blood leukocyte count was significantly
140/90 mmHg or an increase in diastolic pressure of 15
higher (P<0.01) and the blood platelet count was
mmHg or systolic pressure of 30 mmHg compared with
significantly lower (P<0.05) in the preeclampsia group
blood pressures obtained before 20 gestational weeks
than in the uncomplicated pregnancy group at term
and proteinuria ≥0.5 gm/24 hr or ≥30 mg/dl on at least
(Tables 2 and 3).
two occasions more than 6 hours apart.
Women who developed any pregnancy–related
Table 1.
Characteristics of the patients (Mean±SD).
disorder during follow–ups or had any chronic disorders
prior to gestation, multiple gestations or any actue
UNCOMPLICATED
PREECLAMPTIC
infection were excluded from the study. All assays were
(n=25)
(n=15)
performed in a blinded fashion by a physician who was
unaware of the diagnosis.
Age
27.12±4.29
28.86±8.22
Gravidity
2.08±1.12
2.21±2.39
ET–1 concentrations were determined by 125I assay
Parity
0.68±0.80
0.50±0.76
system with AmerlexTM–M magnetic separation
Abortion
0.40±0.76
0.71±2.13
(Amersham, Arlington Heights III) in 45 plasma samples
Gestational age (days)
270.48±9.23
231.00±39.79
from 15 pregnant women who subsequently developed
Birth weight (gr)
3172.00±338.83
2087.14±1099.81
preeclampsia, in 12 plasma samples from 12 preeclamptic
APGAR (5th min)
9.44±0.65
6.00±4.28
pregnant women who were admitted for labor but had
not any had antenatal visit and in 43 plasma samples from
25 randomly chosen women with uncomplicated
The renal function test results the mean systolic and
gestations according to the manufacturer’s protocol, and
diastolic blood pressures and the mean plasma ET–1
evaluated retrospectively.
levels for each 5–week interval by the 20th week of
Results were analyzed by paired student t–test and
gestation are seen in Tables 2 and 3. ET–1 showed no
correlation–regression analysis.
statistically significant correlation with any of the renal
functions tests. No correlations were found between
ET–1 and the weeks of gestation, proteinuria, leukocyte
Results
counts, systolic and diastolic blood pressures (P>0.05).
The mean age, gravidity, parity and number of
There was no significant difference between the groups in
abortions are seen in Table 1. No statistically significant
the means of plasma ET–1 levels at all gestational weeks
difference was determined between the groups (P>0.05).
(P>0.05) except just prior to delivery (P<0.05).
Table 2.
The liver and renal function tests, blood pressures and the plasma ET–1 levels of patients in the uncomplicated pregnancy group
(Mean±SD).
GESTATIONAL AGES (weeks)
20–25
26–30
31–35
At the time of delivery
(n=13)
(n=9)
(n=8)
(n=13)
Systolic BP (mm Hg)
110.62±5.74
113.33±4.92
111.14±7.86
112.92±4.64
Diastolic BP (mmHg)
70.00±5.16
73.33±4.92
71.14±6.53
71.25±5.37
Proteinuria (dipstick)
0
0
0
0
ESBACH (gr/day)
0
0
0
0
Hemoglobin (gr/dl)
11.85±0.76
12.73±1.22
11.02±0.83
11.74±1.23
Leukocytes (count/cc)
8335.38±2016.29
848374±2183.47
8664.72±1954.28
9537.50±2579.11
Platelets (count/cc)
256545.45±51958.37
264927.74±48663.76
235892.83±47374.38
279153.85±10971.88
Urea (mg/dl)
17.90±6.89
17.27±3.83
16.38±3.44
14.27±4.27
Uric acid (mg/dl)
2.65±0.69
2.84±0.26
3.37±1.43
3.84±2.16
Creatinine (mg/dl)
0.54±0.21
0.57±0.27
0.53±0.19
0.51±0.21
ET–1 (pmol/ml)
20.45±11.92
20.70±5.63
22.21±6.45
19.44±9.29
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Y. KİMYA, C. CENGİZ, H. OZAN, L. BÜYÜKUYSAL, S. AYDIN, S. TATLIKAZAN
Table 3.
The liver and renal function tests, blood pressures and the plasma ET–1 levels of patients in the preeclampsia group (Mean±SD).
GESTATIONAL AGES (weeks)
20–25
26–30
31–35
At the time of delivery
(n=15)
(n=14)
(n=11)
(n=15)
Systolic BP (mm Hg)
112.50±12.58
126.67±15.28
165.00±21.21
156.67±32.15
Diastolic BP (mmHg)
77.50±15.00
73.33±5.77
101.34±5.46
109.62±6.42
Proteinuria (dipstick)
0
+++
++
+++
ESBACH (gr/day)
0
2.95±3.18
2.78±1.83
4.37±3.27
Hemoglobin (gr/dl)
11.50±2.45
11.37±3.25
11.35±0.35
12.43±2.03
Leukocytes (count/cc)
7800.00±1131.37
8900.00±1555.63
9287.50±1283.63
15333.33±4932.88
Platelets (count/cc)
216000.00±82024.39
178000.00±8485.28
194586.20±26743.23
201666.67±52880.37
Urea (mg/dl)
16.00±4.24
34.00±5.66
29.46±3.68
22.67±6.66
Uric acid (mg/dl)
4.45±3.18
6.80±3.82
4.96±2.78
6.25±1.91
Creatinine (mg/dl)
0.66±0.49
0.75±0.49
0.46±0.37
0.80±0.42
ET–1 (pmol/ml)
20.84±8.89
23.25±11.01
23.56±64.68
26.55±7.99
Discussion
resistance and decrease renal perfusion and hence the
Although preeclampsia is a major cause of obstetric
glomerular filtration rate in animal experiments (10–12).
and perinatal morbidity, the pathophysiology is still
However, Schiff et al. and Clark et al. did not find any
obscure (5). The vascular endothelium is possibly involved
correlation with blood pressure, proteinuria and
in the etiology of the disease (1, 2). The recently
gestational age (7, 12). In our study, no relationships
discovered endothelium–derived peptide, ET–1, is a very
were found between plasma ET–1 levels and blood
potent vasoconstrictor and plays an important role in the
pressure, proteinuria and gestational age as well as renal
course of essential hypertension (6). Many studies up to
function parameters, white blood cell and thrombcyte
now have demonstrated elevated plasma levels of ET–1 in
counts in our study. This is similar to the findings of
preeclampsia (7), that ET–1 may play an important role
Taylor et al., who observed no correlation of ET–1 with
in the pathophysiology of preeclampsia, either by acting
gestational age, maternal age, parity, thrombocyte count,
on vascular smooth muscle directly to induce contraction
serum creatinine, proteinuria, serum uric acid and mean
or by increasing the formation of angiotensin II, to which
arterial pressure (13).
there is an increased vasopressor response in
Although ET–1 has been suggested to play role to
preeclampsia (8, 9).
take a part in the pathogenesis of preeclampsia, our
In our study we did not find any significant elevation
findings do not support this hypothesis. Though it
of plasma ET–1 in preeclampsia with respect to
increase significantly at the time of delivery, by which
uncomplicated gestations at all gestational weeks but at
time preeclampsia had already developed, there were no
the time of delivery (Tables 2 and 3). However, one
correlations between the plasma ET–1 level and the
should keep in mind that ET–1 elicits a contractile
severity of disease and the gestational week in our study.
response in arteries with damaged endothelium, and the
Therefore we believe that ET–1 is not predictive in
severity of the damage in preeclampsia may potentiate
preeclampsia and probably has a complementary rather
the effect of ET–1 (3).
than an etiological role in its pathophysiology.
In order to estimate the importance of ET–1 levels in
Corresponding author:
pregnancy, its correlation with patient characteristics is of
Yalçın Kimya,
great value. Because it is one of the major
İhsaniye Mahallesi
vasoconstrictors in the circulation, ET–1 might limit renal
Dört Yıldız Sitesi
blood flow, an effect which is expected to be worse in
A2 Blok, No: 4
preeclampsia. ET infusion was shown to increase vascular
BURSA
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The Role of Plasma Endothelin-1 in Preeclampsia
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