Local and systemic estradiol-17β: Effects on uterine and systemic vasodilation

Systemic estradiol-17β (E₂β) administration increases uterine blood flow (UBF), cardiac output (CO), heart rate (HR), and plasma renin activity (PRA). We sought to determine if the E₂β-induced systemic responses were dependent on the observed uterine responses. Nonpregnant, ovariectomized ewes (n = 5) received 3 μg E₂β into both uterine arteries followed 120 min later by systemic E₂β, 1 μg/kg. At 120 min after local E₂β, UBF increased from 26 ± 5 to 161 ± 21 ml/min (P < 0.05); uterine vascular resistance (UVR) decreased 83 ± 2.5% (P < 0.05); and systemic parameters were unchanged. At 120 min after systemic E₂β, UBF remained elevated and CO had increased gradually from 4.4 ± 0.2 to 5.5 ± 0.32 l/min (26 ± 3.4%, P < 0.05), reflecting a 37 ± 3.9% (P < 0.05) increase in HR, mean arterial pressure (MAP) remained unchanged. The increased CO was associated with a 20 ± 3.1% (P < 0.05) fall in systemic vascular resistance (SVR), with %ΔSVR < %ΔUVR (P < 0.05). Base-line PRA and angiotensin II, 1.31 ± 0.2 ng · ml^-1 · h^-1 and 10.3 ± 2.1 pg/ml, respectively, were unchanged by local E₂β; systemic E₂β caused increases to 3.56 ± 0.51 ng · ml^-1 · h^-1 (P < 0.05) and 34.1 ± 11.3 pg/ml (P < 0.05), respectively. E₂β-induced uterine hyperemia occurs independent of its systemic effects and is not responsible for systemic cardiovascular alterations, and the relative uterine vascular responses exceed systemic responses. Systemic responses, e.g., heart rate-mediated increases in CO, are associated with maintenance of MAP, decreases in SVR, and increases in PRA and angiotensin II that are not of uterine origin.