title: The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy.
abstract: Vascular refractoriness to the systemic pressor effects of angiotension II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable animal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P less than 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects of AII, requiring 0.016 microgram of AII/min per kg to elicit a 20 mm HG rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P less than 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses of AII less than 0.016 microgram/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007263:Infusions, Parenteral; D011247:Pregnancy; D012039:Regional Blood Flow; D012756:Sheep; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects
chemical_list: D000804:Angiotensin II