EFFECT OF ENDOTHELIN-1 ON THE UTERINE VASCULATURE OF THE PREGNANT AND ESTROGEN-TREATED NONPREGNANT SHEEP

OBJECTIVE: This study was designed to evaluate the uterine vascular responses to endothelin-1 in pregnant and estrogen-treated nonpregnant sheep. STUDY DESIGN: Seven pregnant and five nonpregnant oophorectomized ewes received local uterine artery infusions of endothelin-1, norepinephrine, and phenylephrine. Arterial blood pressure, heart rate, and uterine blood flow were recorded. RESULTS: Endothelin-1 (0.01 to 3.0 mug/min), norepinephrine (0.1 to 3 mug/min), and phenylephrine (0.1 to 10 mug) produced significant dose-related decreases in uterine blood flow and increases in uterine vascular resistance. On a nanomoles infused per minute basis, endothelin-1 was much more potent than norepinephrine and phenylephrine as a uterine artery vasoconstrictor in both pregnant and nonpregnant sheep. The uterine vascular responses to norepinephrine and phenylephrine were similar in pregnant and nonpregnant ewes, whereas response to endothelin-1 was blunted in pregnancy. CONCLUSION: Endothelin-1 is an extremely potent uterine vasoconstrictor in both pregnant and nonpregnant ewes, but the uterine vascular responsiveness to endothelin-1 is decreased in pregnancy.