Effects of angiotensin II in fetal sheep and modification of its actions by indomethacin

• Published in: The Journal of physiology 1995-08, Vol.487 (Pt 1), p.147-158
• Main Authors: Stevenson, K M, Lumbers, E R
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Blood Pressure - drug effects; Female; Fetus - drug effects; Indomethacin - pharmacology; Infusions, Intravenous; Placenta - blood supply; Pregnancy; Pregnancy, Animal - drug effects; Regional Blood Flow - drug effects; Sheep - embryology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1995.sp020867

1. Angiotensin II (AII) was infused I.V. into seven chronically catheterized fetal sheep (gestational age, 120-136 days). The effects of short-term infusions of 6 and 12 micrograms kg-1 h-1 for 1.5 h were compared with the effects of infusing 6 micrograms kg-1 h-1 for 3 or 5 days (long-term infusion). AII produced an immediate rise in fetal arterial blood pressure (P < 0.025). When infused for 3 or 5 days, 6 micrograms kg-1 h-1 AII caused a greater increase in arterial blood pressure (P < 0.05). 2. Infusions of 6 micrograms kg-1 h-1 AII for 1.5 h had no effect on fetal placental blood flow or on flow to the fetal membranes, but after AII infusion for 3 or 5 days both flows were reduced (P < 0.01 and P < 0.005, respectively). Fetal blood gas status and pH were maintained. The only change in fetal renal function observed with short-term infusions of AII was a rise in sodium excretion when 12 micrograms kg-1 h-1 AII was given (P < 0.05). Infusion of 6 micrograms kg-1 h-1 for 3 or 5 days also caused a rise in sodium excretion (P < 0.025) because total and proximal fractional sodium reabsorptions were depressed (P < 0.01). Infusions of AII had no effects on the volume of lung liquid produced or on its composition. 3. Administration of indomethacin to the ewe (10 mg kg-1) and to the fetus (12 mg kg-1), during the infusion of AII, caused a rise in maternal arterial pressure (P < 0.01) but no change in fetal arterial pressure. 4. After indomethacin, umbilicoplacental blood flow rose (P < 0.05), as did fetal arterial PO2 (P < 0.05). Fetal arterial PCO2, pH and bicarbonate levels fell (P < 0.01). Glomerular filtration rate (GFR) rose (P < 0.01); there was a natriuresis (P < 0.01), chloriuresis (P < 0.01) and a kaliuresis (P < 0.05) but urine flow rate did not change. Lung liquid flow fell (P < 0.01). 5. It is concluded that in the fetus, long-term infusions of AII at a constant dose rate cause a progressive rise in arterial pressure. In addition, effects of AII on placental blood flow and on renal function develop. Thus, short-term infusions of AII cannot be used to predict the renal and cardiovascular effects of sustained high levels of this peptide in the fetus.