o_1977r8vv9vk1ts2ms0kd8pksa.pdf

a Chapter 17 Doppler Velocimetry of the Uteroplacental Circulation During Early Pregnancy 261
Fig. 17.9. Increases in uterine blood flow
as percent of maximum response to estradiol-17b
(E 2 )1lg/kg plotted against
time. Beginning at 120 min after E 2 , L-nitroarginine
methylester (L-NAME), a nitric
oxide synthetase inhibitor, was administered
as an intraarterial bolus injection of
increasing doses. UBF, uterine blood flow.
(Reprinted from [64) with permission)
Adaption of
the immune system
Ingrowth of
endovascular
trophoblast
Destruction of:
The muscle layer of the
spiral arteries
The innervation of the
spiral arteries
Fig. 17.10. Factors leading to vasodilation of the
uteroplacental circulation in normotensive pregnancy.
(From [130] with permission)
Increased synthesis
of EDRF + PGI 2
Vasodilation of the
uteroplacental circulation
Indirect evidence supports both mechanisms. Compounds
that are known to release EDRF (e.g., acetylcholine,
bradykinin, histamine) increase uterine
blood flow when infused directly into the uterine vascular
bed of chronically instrumented sheep [62, 63].
Acetylcholine increases uterine vascular conductance
in nonpregnant and pregnant sheep [63]. Also, local
injection of L-arginine analogs causes local decreases
in uterine blood flow while avoiding alterations in
blood pressure that could directly influence uterine
blood flow [69].
An important observation in this regard was the
finding that estradiol-17b-induced increases in uterine
blood flow are mediated by nitric oxide [64].
Moreover, L-NEMA antagonizes the vasodilating effects
of estradiol-17b on the uterine vasculature in a
dose-dependent manner [64] (Fig. 17.9). This antagonism
of estrogen-induced vasodilation demonstrates
that nitric oxide is important for mediating the vasodilating
effect of estradiol-17b, and it could play a
role in regulating uterine and possibly uteroplacental
blood flow during pregnancy.
When administered systemically, L-arginine analogs
increase blood pressure and reverse pregnancyinduced
refractoriness to vasopressor agents [65].
These observations support the notion that blunted
pressor responsiveness during normal gestation is
due largely to increased elaboration of endotheliumderived
nitric oxide, which also plays a key role in
regulating blood pressure during pregnancy. It has
been demonstrated that endothelium-derived relaxing
factors (e.g., prostacyclin and EDRF) reduce the con-