Fetal and maternal plasma atrial natriuretic factor responses to angiotensin II infusion.

Plasma atrial natriuretic factor and angiotensin II have opposing actions in the regulation of body fluid homeostasis and systemic blood pressure. Angiotensin II infusions stimulate atrial natriuretic factor release in some, but not all, studies in adult mammals. To examine the response during the perinatal period, graded intravenous angiotensin II infusions were administered to four chronically instrumented pregnant ewes and fetuses (132 +/- 1 days of gestation). Fetuses received successive 20-minute intravenous angiotensin II infusions at 25, 50, and 100 ng/kg/min. After a 90-minute recovery, maternal ewes received successive 20-minute angiotensin II infusions (5, 10, and 25 ng/kg/min). During the fetal infusions, mean (+/- SEM) fetal arterial blood pressure (47 +/- 2 to 61 +/- 2 mm Hg, p less than 0.05) and heart rate (155 +/- 16 to 196 +/- 36 beats/min, p less than 0.05) increased, although there was no change in maternal measured parameters. In response to the maternal infusion, maternal mean arterial blood pressure increased (92 +/- 7 to 110 +/- 8 mm Hg, p less than 0.05) and maternal heart rate decreased (136 +/- 4 to 125 +/- 2 beats/min, p less than 0.05) without change in fetal parameters. Fetal plasma atrial natriuretic factor levels (210 +/- 27 to 664 +/- 250 pg/ml, p less than 0.05) significantly increased during the fetal angiotensin II infusions in spite of no change in maternal plasma atrial natriuretic factor (85 +/- 21 to 124 +/- 22 pg/ml) during the maternal angiotensin II infusions. These findings indicate that similar increases in systemic blood pressure in response to angiotensin II infusions stimulate increased fetal, but not maternal, plasma atrial natriuretic factor.

Fetal and maternal response to intravenous infusion of a thromboxane synthetase inhibitor.

Pharmacologic inhibition of thromboxane synthetase activity has reversed the clinical manifestations of toxemia in the ovine model. To investigate placental transfer and fetal effects of a selective thromboxane synthetase inhibitor, CGS13080 (Ciba-Geigy, Summit, N.J.) was intravenously infused into eight singleton- or twin-bearing ewes near term. During CGS 13080 infusion (0.1 mg/kg/hr), maternal steady-state CGS 13080 levels of 102 +/- 18 ng/ml were achieved within 30 minutes and maternal serum thromboxane generation decreased significantly (13 +/- 3 to 4 +/- 1 ng/ml). However, fetal serum levels of CGS 13080 were only 4% of peak maternal concentrations and fetal serum thromboxane generation did not change. There was no evidence of change in uterine blood flow, maternal or fetal blood pressure, heart rate, blood gas values, or fetal or maternal metabolites of prostacyclin or prostaglandin E2 during the study. We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy-induced hypertension.