Human and ovine pregnancies are associated with increases in plasma levels of estrogens and angiotensin II (ANG II), cardiac output (CO), blood volume (BV), and uterine blood flow (UBF), as well as attenuated ANG II pressor responses. We hypothesized that, in nonpregnant animals, prolonged estradiol-17 beta (E2 beta) treatment would reproduce these endocrine and hemodynamic alterations. Nonpregnant ovariectomized ewes (n = 5) received 5 microgram E2 beta/kg iv followed by 220 micrograms/day for 14 days. Plasma E2 beta increased from 36 +/- 6 to 269 +/- 79 (SE) pg/ml (P < 0.05) during E2 beta treatment, returning to control values 4 days posttreatment. By 3 days of E2 beta, mean arterial pressure (MAP) and systemic vascular resistance (SVR) fell 9 +/- 1 and 29 +/- 1%, whereas heart rate (HR) and CO increased 20 +/- 5 and 26 +/- 1% (P < 0.05). Stroke volume (SV), BV, and plasma volume were unchanged until 7 days of E2 beta, with values rising 17 +/- 5, 13 +/- 3, and 14 +/- 4, respectively (P < 0.05). Although MAP remained similarly depressed (-11 +/- 1%) during week 2 of E2 beta, SVR decreased further (-37 +/- 3%) and was associated with additional increases (P < 0.05) in CO to 44 +/- 5%, reflecting rises in SV (21 +/- 2%) but not HR. Increases in BV correlated with rises in CO (r = 0.55) and SV (r = 0.64) but not HR (r = -0.04).(ABSTRACT TRUNCATED AT 250 WORDS)