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

Abstract

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 less than 0.05). The response in UBF was bidirectional, with increases at doses less than or equal to 1.15 microgram/min and decreases at greater than or equal to 2.29 micrograms/min (P less than 0.05). Increases in UBP occurred when the relative rise (delta) in MAP greater than delta UVR, whereas UBF was unchanged when delta MAP = delta UVR and decreased when delta MAP less than delta UVR. SVR also rose in a dose-dependent fashion (P less than 0.05); delta SVR was greater than delta UVR at doses less than or equal to 2.29 micrograms [Val5] ANG II/min (P less than 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 greater than or equal to 2.29 micrograms/min and increases at doses less than 2.29 micrograms/min. The relationship between the changes in MAP and UVR to the response of UBF was as noted above. It is evident that (a) [Val5] NAG II is 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.