Effects of indomethacin on sheep uteroplacental circulations and sensitivity to angiotensin II.

Indomethacin, a prostaglandin synthetase inhibitor, injected simultaneously into the abdominal aorta of the ewe and her fetus at 125 days' gestation causes vasoconstriction of both the uterine and umbilical circulations. There is no change in these hemodynamic effects of indomethacin in the presence of phenoxybenzamine, an alpha-adrenergic antagonist. When the indomethacin experiment is repeated seven to 10 days later, a uterine vasoconstriction 10 per cent greater than that found earlier occurs, but there is no change from control umbilical vascular resistance. The mean maternal arterial pressure response (20 mm. Hg) to angiotensin II with and without indomethacin also was examined at the same time in gestation. Indomethacin infusion to the ewe significantly reduces the pressor dose (nanograms per kilogram per minute) by 42 +/- 4 per cent. Thus, in pregnant sheep in the third trimester, endogenous prostaglandins appear to be: (1) partial determinants of basal blood flow in both the uterine and umbilical circulations and (2) modulators of the vasoconstrictive effects of angiotensin II in the ewe.