UTERINE PROSTAGLANDIN PRODUCTION IN OVINE PREGNANCY - EFFECTS OF ANGIOTENSIN-II AND INDOMETHACIN

The ovine and human uteroplacental vascular beds are more refractory to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. ANG II increases in vitro prostacyclin (PGI2) production by uterine but not omental arteries from pregnant sheep. Thus vasodilator prostaglandins may account for this difference in vascular responsiveness. We measured uterine and systemic eicosanoid production and hemodynamic responses in pregnant sheep before and during intravenous ANG II (1.15 and 11.5-mu-g/min). ANG II caused dose-related increases in arterial pressure and systemic and uterine vascular resistance (P < 0.05). PGI2 metabolite (6-keto-PGF1-alpha) in the uterine vein rose from 166 +/- 70 (SE) to 223 +/- 114 and 631 +/- 323 pg/ml, respectively (P < 0.05), and arterial levels increased from 67 +/- 24 to 145 +/- 78 and 312 +/- 173 pg/ml, respectively (P < 0.05). Basal uterine venoarterial differences of 6-keto-PGF1-alpha were 99 +/- 43 pg/ml and increased during 11.5-mu-g ANG II/min to 295 +/- 181 pg/ml (P < 0.05) but not during 1.15-mu-g/min (64 +/- 30 pg/ml). Responses were similar in gravid and nongravid uterine horns. Unilateral uterine prostaglandin inhibition with indomethacin did not alter basal uterine blood flow or systemic responses to ANG II (0.573-11.5-mu-g/min); however, ipsilateral uterine prostaglandin production fell and uterine vasoconstrictor responses increased (P < 0.05). During ovine pregnancy ANG II increases uterine PGI2 production. PGI2 appears in part to attenuate ANG II-induced uterine vasoconstriction.