Endothelium-derived vasodilator production by ovine uterine and
systemic arteries: i. effects of angiotensin ii on prostacyclin and
nitric oxide in pregnancy.
Magness, Ronald R., Charles R. Rosenfeld, Abdullah Hassan, and Philip
W. Shaul.
Departments of Pediatrics and Obstetrics and Gynecology, University
of Texas Southwestern Medical Center, Dallas, Texas 75235-9063
APStracts 2:0472H, 1995.
Pregnancy is associated with uterine vasodilation and reduced systemic
pressor responses to infused angiotensin II (ANG II). The uterine
vasculature is less responsive than the systemic vasculature to ANG
II-induced vasoconstriction. We hypothesized that pregnancy augments
basal and ANG II-stimulated uterine and systemic artery endothelium
-derived prostacyclin (PGI2) and/or nitric oxide (NO) production,
which are released locally to increase the vascular smooth muscle
(VSM) second messengers cyclic adenosine and guanosine monophosphate
(cAMP and cGMP), respectively. Uterine and omental (systemic) artery
segments from pregnant and nonpregnant sheep were incubated in Krebs
-Henseleit solution with 100[mu]M isobutylmethyxanthine (IBMX). Basal
PGI2, cAMP, and cGMP production was 2.4-, 1.6-, and 5.9-fold,
respectively, greater (p<0.01) in uterine arteries from pregnant
versus nonpregnant sheep; endothelium removal lowered (p<0.05)
values 69%, 44% and 88%. Basal systemic artery PGI2 and cAMP, but not
cGMP, also were elevated during pregnancy. In all arteries studied,
indomethacin (INDO; 100[mu]M) decreased PGI2 and cAMP, but not cGMP
production, while L-nitro-arginine methyl ester (L-NAME; 10[mu]M) and
methylene blue (MB,10[mu]M) only decreased cGMP. Basal uterine, but
not systemic artery NO synthase activity, assessed by measuring
conversion of 3H-arginine to 3H-citrulline, was 1.8-fold higher
(p<0.01) in pregnancy and decreased (p<0.01) 77% and 74%
after endothelium removal and with L-NAME. ANG II (50 nM) increased
PGI2 (86%) and cAMP (56%) production only in uterine arteries from
pregnant sheep (p<0.05); this was abolished by endothelium
removal or INDO. ANG II also increased (p<0.01) cGMP production
by uterine arteries from both groups, but only by systemic arteries
from pregnant ewes; this was absent in denuded, L-NAME or MB treated
vessels. Stimulation of VSM cGMP production with sodium nitroprusside
(50[mu]M) was inhibited by MB, but not L-NAME or endothelium removal.
In ovine pregnancy, endothelium-derived PGI2 and NO production are
enhanced and may contribute to attenuated ANG II-induced
vasoconstriction by modulating VSM cAMP and cGMP.
Received 13 February 1995; accepted in final form 5 October 1995.
APS Manuscript Number H130-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95