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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical