Systemic and uterine responsiveness to angiotensin II and norepinephrine in estrogen-treated nonpregnant sheep

Abstract

Pregnancy is associated with uterine and systemic vasodilation and reduced vascular reactivity to angiotensin II and perhaps norepinephrine. The uteroplacental vasculature is relatively refractory to angiotensin II but very sensitive to norepinephrine. To investigate the possible role of the high levels of estrogen in pregnancy mediating these hemodynamic changes, we examined systemic and uterine vascular responsiveness to angiotensin II and norepinephrine in eight chronically instrumented nonpregnant sheep treated with 17β-estradiol. In these animals, 17β-estradiol produced significant systemic and uterine vasodilation without changing arterial pressure; cardiac output increased from 5.3 ± 0.3 to 6.7 ± 0.4 L/min, and uterine blood flow increased from 26 ± 3 to 218 ± 13 ml/min (mean ± SE). Treatment with 17β-estradiol reduced the increases in systemic vascular resistance produced by angiotensin II and norepinephrine by 25% and 35%, respectively. After 17β-estradiol treatment, the uterine vascular responses were compared to the systemic vascular responses; the uterine responses to angiotensin II were only half the systemic responses, whereas the uterine responses to norepinephrine were six times greater than the systemic responses and were associated with decreases in uterine blood flow of 35% to 40%. These hemodynamic features of nonpregnant sheep treated with estrogen are strikingly similar to previous observations in sheep during pregnancy.