الفهرس 
HypertensionOnly 14 pages are availabe for public view
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Abstract
Hypertension (HY) disorder during pregnancy is one
of the most common medical problems in pregnancy. HY
may complicate 10–15% of pregnancies. It is a major cause
of maternal and perinatal morbidity and mortality,
worldwide. The initiating event is reduced utero-placental
perfusion as a result of abnormal invasion of spiral arterioles
by the extravillous cytotrophoblast with consequent
reduction of blood flow to the intervillous space and
associated structural changes in umbilical vessels.
Sildenafil citrate (SC) acts as a potent vasodilator by
selectively inhibiting phosphodiesterase 5 (PDE5), which
enzymatically converts the intracellular second messenger
cGMP into its GTP (inactive form). SC is used recently in
treatment of several diseases such as; pulmonary arterial
hypertension, erectile dysfunction, interauterine growth
retardation and preterm labor. Aldomet (α-methyldopa) is the
classic treatment of hypertension and pregnancy-induced
hypertension for a long time. It is considered by most
clinicians to be the drug of choice in the treatment of
hypertension in pregnancy. Aldomet is responsible for
inducing a number of adverse side effects. These side effects
may be psychological and physiological side effects. So it is contraindicated in many cases such as depression, liver
disease, phaeochromocytoma and breastfeeding women.
The aim of this research was to compare the
therapeutic effect of SC versus traditional antihypertensive
drug (Aldomet) on the vascular channels of the placenta and
umbilical cord in the hypertensive pregnant rat model.
Thirty six adult female albino rats were used in the
study and were divided into six groups. Group I served as
control pregnant rats. Rats in group II were used as a model
of induced HY in pregnant rats by administration of LNAME
in an oral dose 50 mg/kg/d from day 1 to day 19 of
gestation. Rats in group III were used as control pregnant rats
treated SC which was administrated in an oral dose 4
mg/kg/d from day 1 to day 19 of gestation. Rats in group IV
were used as control pregnant rats treated with aldomet
which was administrated in an oral dose 77 mg/day
according to Paget and Barnes formula from day 1 to day 19
of gestation. Rats in group V were used as a model of
induced HY treated with SC. These rats received L-NAME
as described in group II and receiving SC as described in
group III. Rats in group VI were used as a model of induced
HY treated with aldomet. These rats received L-NAME as
described in group II and receiving aldomet as described ingroup IV. Animals were sacrificed on day 20 of gestation;
definitive placenta and umbilical cord specimens were
processed for histological, immunohistochemical
examination and morphometrical measurement.
Microscopic and morphometrical changes were
evident in HY placenta and umbilical cord. The microscopic
placental changes were in the form of congested fetal
capillaries, syncytial knots, syncytiotrophoblastic shedding,
cytotrophoblastic proliferation, thickening of the basement
membrane of trophoblasts, fibrinoid necrosis, infarction,
hyalinization and massive areas of complete necrosis and
degeneration. Umbilical cord changes appeared in the form
of flattening, thinning and disruption of the lining endothelium
of the vein. Umbilical artery apparently showed same
thickness of the wall like control group. However, nuclei of
tunica media layer seemed disorganized and some cells
showed degeneration and necrosis. Morphometrical changes
appeared in the form of decreased perimeter of maternal
sinusoids, elevated blood pressure and decreased both, fetal
and placental weight.
SC treatment in HY group showed remarkable
amelioration of histopathological changes that occured with
HY in the form of normal thickening of trophoblastic basement membrane, lack of syncytial knots,
syncytiotrophoblastic shedding, fibrinoid necrosis and
decreased apoptosis. However, the basal zone showed fewer
areas of fibrinoid necrosis and hyalinization. Umbilical cord
vessels showed normal wall thickness and endothelial linning
with intact layers. Also in the morphometric measurements
there were an increase in perimeter of maternal sinusoids, a
decrease in blood pressure which reached normal value as
control group and an increase in both, fetal and placental
weight.
On the other hand, aldomet showed apparently a slight
amelioration of histopathological changes that occurred with
HY as there were syncytial knots, syncytiotrophoblastic
shedding, thickening in basement membrane of trophblast,
fibrinoid necrosis, hyalinization and degeneration and
necrosis. Morphometrical measurements showed a slight
improvement in blood pressure, fetal and placental weight but
did not reach the normal values as control group.
It is concluded that Sildenafil citrate is more effective
in treatment of hypertension than aldomet. In hypertensive
pregnant rats, aldomet induced mild amelioration of the
deleterious changes in the placenta and umbilical cord while
Sildenafil citrate induced a remarkable improvement in theplacenta and umbilical cord and according to the literatures it
also has no teratogenic or fetotoxic effects. So, according to
these pervious results it might be preferable to be use
Sildenafil citrate in treatment of hypertension with
pregnancy.