Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy.
Uteroplacentral responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANG 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; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1, Ile8]ANG II (AT1 and AT2), losartan (AT1) PD-123319 (AT2), and CGP-42112A (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. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas 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 microM) increased PGI2 synthesis 62%, from 214 +/- 13 to 346 +/- 23 pg.mg-1.h-1 (P < 0.05). Losartan (1.0 microM) inhibited the rise in PGI2 (257 +/- 24 vs. 238 +/- 25 pg.mg-1.h-1), whereas 1.0 microM PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg.mg-1.h-1; 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 UASM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.
Cox
B E
BE
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Rosenfeld
C R
CR
Kalinyak
J E
JE
Magness
R R
RR
Shaul
P W
PW
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D008638:Mesenteric Arteries / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D049590:Postpartum Period; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012016:Reference Values; D012077:Renal Artery / Q000378:metabolism; D012756:Sheep; D014599:Uterus / Q000098:blood supply
D011945:Receptors, Angiotensin; D011464:Epoprostenol