The effects of a converting enzyme inhibitor (Captopril) and angiotensin II on fetal renal function

• Published in: British journal of pharmacology 1993-10, Vol.110 (2), p.821-827
• Main Authors: Lumbers, E.R., Burrell, J.H., Menzies, R.I., Stevens, A.D.
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin II - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Blood Gas Analysis; Captopril; Captopril - pharmacology; Female; glomerular filtration rate; Glomerular Filtration Rate - drug effects; Hemodynamics - drug effects; Kidney - drug effects; Kidney - embryology; Kidney Function Tests; Pregnancy; Sheep; Sodium - urine; sodium excretion
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13886.x

1 Renal function was studied in chronically catheterized fetal sheep (119–128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, Captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2 An i.v. dose of 15 mg (about 319 μg kg−1) of Captopril to salt‐replete ewes followed by an infusion to the ewe of 6 mg h−1 (about 128 μg kg−1 h−1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 ± 5.6 to 84.9 ± 8.3 ml min−1 (mean ± s.e.mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3 Ewes were treated for the next 2 days with 15 mg Captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of Captopril (6 mg h−1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 μg kg−1 h−1 of angiotensin II was infused directly into the fetus RBF fell from 69 ± 10.1 ml min−1 to 31 ± 13.9 ml min−1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4 It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.