Pregnancy causes a decrease in the number and affinity of myometrial angiotensin II receptors.

The pressor response to exogenously infused angiotensin II is decreased in normal human and ovine pregnancy when compared to the nonpregnant state. This study was designed to determine the mechanism for decrease in target organ sensitivity by examining pregnancy-induced changes in the affinity and number of angiotensin II receptors in myometrium from pregnant and nonpregnant sheep. Tissues were obtained from four ovariectomized sheep given 50 micrograms estradiol-17 beta on days 3 and 5 postsurgery and from four pregnant sheep (mean gestational age 136 days). Binding of 125I-angiotensin II was determined in particulate fractions of myometrium prepared by differential centrifugation. The 125I-angiotensin II binding to myometrial preparations was specific, saturable, and linear with protein concentration. In the nonpregnant group, binding capacity for angiotensin II in myometrium was 502 +/- 76 fmol/mg protein, whereas in the pregnant group it was 184 +/- 65 fmol/mg protein (P less than .01). Receptor affinity also was less (Kd 1.72 +/- 0.39 nM) during pregnancy compared with the nonpregnant sheep uterus (3.9 +/- 0.80 nM; P less than .01). These data support the hypothesis that the decrease in target organ sensitivity to exogenously administered angiotensin II during pregnancy in human and ovine species may be secondary to a decrease in the total number and affinity of specific angiotensin II receptors.