Effect of angiotensin II on uterine and systemic vasculature in pregnant sheep

The response of uteroplacental blood flow (UBF) to angiotensin II is controversial. Moreover, the relationship of the uterine and systemic responses to infused angiotensin II is not well understood. Thus, in eight chronically instrumented, near-term pregnant sheep, we have determined the relationships between the dose and duration of constant systemic infusions of angiotensin II ([Val⁵] ANG II) and changes in UBF, uterine vascular resistance (UVR), mean arterial pressure (MAP), and systemic vascular resistance (SVR). [VAL⁵] ANG II caused dose-dependent increases in UVR and MAP at all doses studied (P < 0.05). The response in UBF was bidirectional, with increases at doses ≤ 1.15 μg/min and decreases at ≥ 2.29 μg/min (P < 0.05). Increases in UBF occurred when the relative rise (Δ) in MAP > Δ UVR, whereas UBF was unchanged when Δ MAP = Δ UVR and decreased when Δ MAP < Δ UVR. SVR also rose in a dose-dependent fashion (P < 0.05); Δ SVR was > Δ UVR at doses ≤ 2.29 μg [Val⁵] ANG II/min (P < 0.01). In studies of the effect of duration of [Val⁵] ANG II infusions, UBF increased at all doses during the 1st min, followed by stabilization at 4-5 min, with eventual decreases at doses ≥ 2.29 μg/min and increases at doses <2.29 μg/min. The relationship between the changes in MAP und UVR to the response of UBF was as noted above. It is evident that (a) [Val⁵] ANG II is a uterine vasoconstrictor, (b) changes in UBF are dependent upon relative changes in perfusion pressure and UVR, which in turn are dependent upon both the dose and duration of a [Val⁵] ANG II infusion, and (c) the uteroplacental vasculature is relatively refractory to the vasoconstricting effects of low doses of [Val⁵] ANG II.