ROLE OF ANGIOTENSIN-II AND ALPHA-ADRENERGIC RECEPTORS DURING ESTROGEN-INDUCED VASODILATION IN EWES

Estradiol-17beta (E2beta) produces uterine and systemic vasodilation in nonpregnant ewes without altering mean arterial pressure (MAP). Mechanisms responsible for maintaining MAP and thus uterine blood flow (UBF) may include activation of the renin-angiotensin and/or adrenergic systems. We therefore investigated the effects of systemic blockade of angiotensin II (ANG II) and/or alpha-adrenergic receptors in nonpregnant, castrated ewes, using saralasin (Sar) and/or phentolamine (Phen) in the presence or absence of intravenous E2beta (1.0 mug/kg). In nonestrogenized ewes neither antagonist alone had substantial cardiovascular effects; however, Sar + Phen decreased systemic vascular resistance (SVR) 20 +/- 7.4 %(SE) and increased heart rate (HR) 50 +/- 19% (P < 0.01); MAP and UBF were unaffected. Following E2beta treatment SVR fell 17 +/- 2.4% (P < 0.01), UBF increased more than fourfold, and MAP was unchanged. Compared with E2beta alone, Phen + E2beta decreased SVR 42 +/- 4.7%, and MAP fell 11 +/- 1.8% (P < 0.05) despite 40-50% increases in HR and cardiac output (P < 0.05). Responses to Sar + E2beta were similar to E2beta alone, except for a fall in MAP, whereas responses to Sar + Phen + E2beta resembled those of Phen + E2beta. E2beta-induced uterine vasodilation was unaltered by Sar and/or Phen. During E2beta-induced vasodilation, MAP is maintained by enhanced activation of the a-adrenergic and renin-angiotensin systems; however, uterine vascular responses to E2beta are independent of both systems and perfusion pressure.