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

Uteroplacental 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 11 (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 μM) increased PGI₂ synthesis 62%, from 214 ± 13 to 346 ± 23 pg · mg^-1 · h^-1 (P < 0.05). Losartan (1.0 μM) inhibited the rise in PGI₂ (257 ± 24 vs. 238 ± 25 pg · mg^-1 · h^{- 1}), whereas 1.0 μM 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 UA SM and ANG II- induced increases in UA prostacyclin synthesis by endothelial AT₁ receptors.