Angiotensin II mediates uterine vasoconstriction through α-stimulation

Intravenous angiotensin II (ANG II) increases uterine vascular resistance (UVR), whereas uterine intra-arterial infusions do not. Type 2 ANG II (AT ₂) receptors predominate in uterine vascular smooth muscle; this may reflect involvement of systemic type 1 ANG II (AT₁) receptor-mediated α-adrenergic activation. To examine this, we compared systemic pressor and UVR responses to intravenous phenylephrine and ANG II without and with systemic or uterine α-receptor blockade and in the absence or presence of AT₁ receptor blockade in pregnant and nonpregnant ewes. Systemic α-receptor blockade inhibited phenylephrine-mediated increases in mean arterial pressure (MAP) and UVR, whereas uterine α-receptor blockade alone did not alter pressor responses and resulted in proportionate increases in UVR and MAP. Although neither systemic nor uterine α-receptor blockade affected ANG II-mediated pressor responses, UVR responses decreased >65% and also were proportionate to increases in MAP. Systemic AT₁ receptor blockade inhibited all responses to intravenous ANG II. In contrast, uterine AT₁ receptor blockade + systemic α-receptor blockade resulted in persistent proportionate increases in MAP and UVR. Uterine AT₂ receptor blockade had no effects. We have shown that ANG II-mediated pressor responses reflect activation of systemic vascular AT₁ receptors, whereas increases in UVR reflect AT₁ receptor-mediated release of an α-agonist and uterine autoregulatory responses.