Angiotensin II indirectly vasoconstricts the ovine uterine circulation

The uterine vasculature of women and sheep predominantly expresses type 2 A NG II receptors that do not mediate vasoconstriction. Although systemic ANG II infusions increase uterine vascular resistance (UVR), this could reflec t indirect mechanisms. Thus we compared systemic and local intra-arterial A NG II infusions in six near-term pregnant and five ovariectomized nonpregna nt ewes to determine how ANG II increases UVR. Systemic ANG II dose-depende ntly (P > 0.001) increased arterial:pressure (MAP) and UVR and decreased ut erine blood,flow (UBF) in pregnant and nonpregnant ewes; however, nonpregna nt responses exceeded pregnant (P < 0.001). In contrast, local ANG II infus ions at rates designed to achieve concentrations in the uterine circulation comparable to those seen during systemic infusions did not significantly d ecrease UBF in either group, and changes in MAP and UVR were absent or mark edly attenuated. When MAP rose during local ANG II, which only occurred wit h doses greater than or equal to 2 ng/ml, increases in MAP were delayed mor e than twofold compared with responses during systemic ANG II infusions and always preceded decreases in UBF, resembling that observed during systemic ANG II infusions. These observations demonstrate attenuated uterine vascul ar responses to systemic ANG II during pregnancy and suggest that systemic ANG II may increase UVR through release of another potent vasoconstrictor(s ) into the systemic circulation.