Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy

Uteroplacental responses to infused angiotensin II (ANG Il) 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 (WA), 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 I-125-labeled ANG II binding by [Sar(1),Ile(8)]ANG II (AT(1) and AT(2)), losartan (AT(1)), PD-123319 (AT(2)), and CGP-42112A (AT(2)). AT(2) receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT(1) receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT(2) receptors appear to predominate in media of small intramyometrial arteries, whereas AT(1) receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI(2) synthesis during pregnancy. ANG II (0.05 mu M) increased PGI(2) synthesis 62%, from 214 +/- 13 to 346 +/- 23 pg . mg(-1) . h(-1) (P < 0.05). Losartan (1.0 mu M) inhibited the rise in PGI(2) (257 +/- 24 vs. 238 +/- 26 pg . mg(-1) h(-1)), whereas 1.0 mu M PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg . mg(-1) . h(-1); P < 0.05). AT(2) receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT(2) receptors in UA SM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT(1) receptors.