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 (Us) may demonstrate ANG II receptor (AT receptors) down-regulation or expression of AT(2) receptors, which do not mediate vasocon striction. We determined AT receptor binding characteristics and subtype expression in Us 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 [I-125]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 +/- 129us. 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). AT(1)/AT(2) 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 10(4) N/m(2); 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 AT(1) receptor inhibition. Myometrium from nonpregnant women (n = 3) was unresponsive, and AT(2) inhibition did not alter responses. In nonpregnant women, AT(2) receptors predominate in Ua and myometrium. Although Ua AT receptors are unaltered during pregnancy, myometrial B-max, decreases, reflecting decreases in the expression of AT(2) much greater than AT(1) receptors and differential receptor regulation.