Angiotensin II receptor characteristics and subtype expression in uterine arteries and myometrium during pregnancy

The uteroplacental vasculature is less sensitive to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. Although the mechanism(s) responsible is unclear, uterine arteries (Ua) may demonstrate ANG II receptor (AT receptors) down-regulation or expression of AT₂ receptors, which do not mediate vasoconstriction. We determined AT receptor binding characteristics and subtype expression in Ua from normotensive pregnant (n = 14; 38 ± 0.5 weeks gestation) and nonpregnant (n = 28) women. Comparative studies were performed with myometrium, a nonvascular smooth muscle. We measured binding density (B(max)) and affinity (K(d)) in plasma membrane preparations employing radioligand binding. Receptor subtypes were assessed by inhibiting [¹²⁵I]ANG II binding with specific antagonists. During pregnancy, the Ua B(max) and K(d) were unchanged (P > 0.1; 221 ± 36 vs. 159 ± 27 fmol/mg protein and 0.8 ± 0.1 vs. 0.9 ± 0.1 nmol/L, respectively). However, myometrial B(max) decreased 92% (580 ± 129 vs. 44 ± 7 fmol/mg protein; P < 0.001), and K(d) rose 4-fold (1.5 ± 0.4 to 6.0 ± 0.6 nmol/L; P < 0.001). AT₁/AT₂ expression averaged 15%/85% in Ua from nonpregnant and pregnant women, whereas in myometrium, values were 10%/90% and 60%/40%, respectively. In myometrium from laboring women (n = 8), force (1.38 ± 0.14 to 1.59 ± 0.12 x 10⁴ N/m²; P < 0.04) and contractile frequency (0.038 ± 0.05 to 0.116 ± 0.014 contractions/min; P < 0.001) increased with 10^-6 mol/L ANG II and were abolished by AT₁ receptor inhibition. Myometrium from nonpregnant women (n = 3) was unresponsive, and AT₂ inhibition did not alter responses. In nonpregnant women, AT₂ receptors predominate in Ua and myometrium. Although Ua AT receptors are unaltered during pregnancy, myometrial B(max) decreases, reflecting decreases in the expression of AT₂ >> AT₁ receptors and differential receptor regulation.