Effect of captopril on uterine blood flow and prostaglandin E synthesis in the pregnant rabbit

Captopril, 5 mg/kg, administered to pregnant rabbits caused a reduction in mean arterial pressure (MAP) from 106 ± 2 to 87 ± 2 mmHg (P < 0.01) without change in cardiac output or renal blood flow. Uterine blood flow fell from 31.9 ± 2.5 to 21.3 ± 3.4 ml/min (P < 0.01) as uterine vein prostaglandin E series level (PGE) decreased from 127 ± 23 ng/ml to 26 ± 8 ng/ml (P < 0.01). Saralasin also caused a reduction in MAP from 110 ± 5 to 92 ± 4.3 (P < 0.01), a reduction in uterine blood flow from 28.8 ± 1.6 to 21.8 ± 1.7 ml/min (P < 0.01) as uterine vein PGE decreased from 121.3 ± 14.4 to 63.5 ± 14.2 ng/ml (P < 0.01). Plasma renin activity (PRA) was higher in the uterine vein, 11 ± 3 ng/ml per h, than peripheral vein, 6 ± 1.6 ng/ml per h, (P < 0.05), before Captopril and rose in the uterine vein to 90 ± 19 ng/ml per h (P < 0.01) as peripheral vein PRA rose to 62 ± 15 ng/ml pr h (P < 0.005) after Captopril. After saralasin uterine vein PRA rose from 4.6 ± 1.5 to 14.8 ± 6.3 ng/ml per h (P < 0.05) and peripheral vein PRA rose from 3.7 ± 1 to 6.5 ± 2.1 (P < 0.05). Reducing MAP with MgSO₄ from 98 ± 4 to 70 ± 2 (P < 0.01) caused a significant fall in cardiac output from 695 ± 33 to 588 ± 49 (P < 0.01) without change in renal or uterine blood flow. Uterine vein PGE concentration also did not change significantly following MgSO₄; 80 ± 22 ng/ml before and 60 ± 27 ng/ml (NS) during the administration of MgSO₄. Chronic administration of Captopril in doses of either 2.5 or 5.0 mg/kg per d from the 15th d of gestation caused an 86% fetal mortality at the lower and a 92% fetal mortality at the higher dose of the drug. These experiments point to the importance of uterine PGE synthesis in maintenance of uterine blood flow and fetal survival during pregnancy and suggest that uterine PGE synthesis is dependent upon angiotensin II. Synthesis of uterine renin and PGE may be necessary for maintenance of uterine blood flow and fetal survival during pregnancy.