Tissue specific expression of vascular smooth muscle angiotensin ii
receptor subtypes during ovine pregnancy 1.
Cox, Blair E., Charles R. Rosenfeld, Judith E. Kalinyak, Ronald R.
Magness, and Philip W. Shaul.
Department of Pediatrics, UT Southwestern Medical Center, Dallas,
TX 75235 and Department of Internal Medicine, University of
California, San Francisco, San Francisco, CA 94110
APStracts 2:0543H, 1995.
Uteroplacental responses to infused angiotensin II (ANG II) are less
than those elicited by systemic vasculature. This does not reflect
angiotensin II receptor (AT) downregulation, but may reflect
differences in AT receptor subtypes expressed. We examined AT
receptor subtypes in smooth muscle (SM) from uterine (Ua),
mesenteric, renal, and mammary arteries, and aorta from nulliparous
(n=12), pregnant (n=18; 105-140d, term=145d), postpartum (n=5; 6-9d
after delivery), and nonpregnant parous (n=14) ewes by assessing
displacement of [125I]-ANG II binding by [Sar1,Ile8]-ANG II (AT1 and
AT2), losartan (AT1), PD123319 (AT2), and CGP42112A (AT2). AT2
receptors accounted for 75-90% of total binding in Ua. Except for
mammary arteries, other arteries expressed only AT1 receptors.
Receptor subtype expression was not altered by reproductive state in
any artery studied. Using autoradiography, AT2 receptors appear to
predominate in media of small intramyometrial arteries while AT1
receptors predominate in the luminal portion. We, therefore,
determined which subtype mediates endothelium-derived ANG II-induced
increases in Ua PGI2 synthesis during pregnancy. ANG II (0.05 _M)
increased PGI2 synthesis 62%, from 214+/-13 to 346+/-23 pg/mg x h
(p<0.05). Losartan (1.0 _M) inhibited the rise in PGI2 (257+/-24
vs 238+/-25 pg/mg x h), whereas 1.0?[mu]M PD123319 had no effect
(231+/-23 vs 337+/-31 pg/mg x h; p<0.05). AT2 receptors do not
mediate ANG II-induced vasoconstriction, thus differences in
uteroplacental and systemic sensitivity to ANG II may reflect
predominance of AT2 receptors in Ua SM and ANG II-induced increases
in Ua prostacyclin synthesis by endothelial AT1 receptors.
Received 31 March 1995; accepted in final form 29 November 1995.
APS Manuscript Number H313-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95