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. 1995 May;39(5):497–501. doi: 10.1111/j.1365-2125.1995.tb04486.x

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

R de Moura 1, M A Lopes 1
PMCID: PMC1365056  PMID: 7669485

Abstract

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Albertini R., Seino M., Scicli A. G., Carretero O. A. Uteroplacental renin in regulation of blood pressure in the pregnant rabbit. Am J Physiol. 1980 Aug;239(2):H266–H271. doi: 10.1152/ajpheart.1980.239.2.H266. [DOI] [PubMed] [Google Scholar]
  2. Binder N. D., Faber J. J. Effects of captopril on blood pressure, placental blood flow and uterine oxygen consumption in pregnant rabbits. J Pharmacol Exp Ther. 1992 Jan;260(1):294–299. [PubMed] [Google Scholar]
  3. Boutroy M. J., Vert P., Hurault de Ligny B., Miton A. Captopril administration in pregnancy impairs fetal angiotensin converting enzyme activity and neonatal adaptation. Lancet. 1984 Oct 20;2(8408):935–936. doi: 10.1016/s0140-6736(84)90695-0. [DOI] [PubMed] [Google Scholar]
  4. Broughton Pipkin F., Smales O. R. A study of factors affecting blood pressure and angiotensin II in newborn infants. J Pediatr. 1977 Jul;91(1):113–119. doi: 10.1016/s0022-3476(77)80460-5. [DOI] [PubMed] [Google Scholar]
  5. Broughton Pipkin F., Turner S. R., Symonds E. M. Possible risk with captopril in pregnancy: some animal data. Lancet. 1980 Jun 7;1(8180):1256–1256. doi: 10.1016/s0140-6736(80)91723-7. [DOI] [PubMed] [Google Scholar]
  6. Caraman P. L., Miton A., Hurault de Ligny B., Kessler M., Boutroy M. J., Schweitzer M., Brocard O., Ragage J. P., Netter P. Grossesses sous captopril. Therapie. 1984 Jan-Feb;39(1):59–62. [PubMed] [Google Scholar]
  7. Ferris T. F., Stein J. H., Kauffman J. Uterine blood flow and uterine renin secretion. J Clin Invest. 1972 Nov;51(11):2827–2833. doi: 10.1172/JCI107105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferris T. F., Weir E. K. Effect of captopril on uterine blood flow and prostaglandin E synthesis in the pregnant rabbit. J Clin Invest. 1983 Apr;71(4):809–815. doi: 10.1172/JCI110834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fiocchi R., Lijnen P., Fagard R., Staessen J., Amery A., Van Assche F., Spitz B., Rademaker M. Captopril during pregnancy. Lancet. 1984 Nov 17;2(8412):1153–1153. doi: 10.1016/s0140-6736(84)91581-2. [DOI] [PubMed] [Google Scholar]
  10. Félétou M., Germain M., Teisseire B. Converting-enzyme inhibitors potentiate bradykinin-induced relaxation in vitro. Am J Physiol. 1992 Mar;262(3 Pt 2):H839–H845. doi: 10.1152/ajpheart.1992.262.3.H839. [DOI] [PubMed] [Google Scholar]
  11. Keith I. M., Will J. A., Weir E. K. Captopril: association with fetal death and pulmonary vascular changes in the rabbit. Proc Soc Exp Biol Med. 1982 Jul;170(3):378–383. doi: 10.3181/00379727-170-41446. [DOI] [PubMed] [Google Scholar]
  12. Lumbers E. R., Kingsford N. M., Menzies R. I., Stevens A. D. Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus. Am J Physiol. 1992 May;262(5 Pt 2):R754–R760. doi: 10.1152/ajpregu.1992.262.5.R754. [DOI] [PubMed] [Google Scholar]
  13. Lüscher T. F., Boulanger C. M., Dohi Y., Yang Z. H. Endothelium-derived contracting factors. Hypertension. 1992 Feb;19(2):117–130. doi: 10.1161/01.hyp.19.2.117. [DOI] [PubMed] [Google Scholar]
  14. Melmon K. L., Cline M. J., Hughes T., Nies A. S. Kinins: possible mediators of neonatal circulatory changes in man. J Clin Invest. 1968 Jun;47(6):1295–1302. doi: 10.1172/JCI105821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Millar J. A., Wilson P. D., Morrison N. Management of severe hypertension in pregnancy by a combined drug regimen including captopril: case report. N Z Med J. 1983 Oct 26;96(742):796–798. [PubMed] [Google Scholar]
  16. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  17. Rosenfeld C. R., Naden R. P. Uterine and nonuterine vascular responses to angiotensin II in ovine pregnancy. Am J Physiol. 1989 Jul;257(1 Pt 2):H17–H24. doi: 10.1152/ajpheart.1989.257.1.H17. [DOI] [PubMed] [Google Scholar]
  18. Shotan A., Widerhorn J., Hurst A., Elkayam U. Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use. Am J Med. 1994 May;96(5):451–456. doi: 10.1016/0002-9343(94)90172-4. [DOI] [PubMed] [Google Scholar]
  19. Soares de Moura R., Solano Vale N. Effect of captopril on bradykinin inactivation by human foetal placental circulation. Br J Clin Pharmacol. 1986 Feb;21(2):143–148. doi: 10.1111/j.1365-2125.1986.tb05168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Still J. G., Greiss F. C., Jr The effect of prostaglandins and other vasoactive substances on uterine blood flow and myometrial activity. Am J Obstet Gynecol. 1978 Jan 1;130(1):1–8. doi: 10.1016/0002-9378(78)90430-1. [DOI] [PubMed] [Google Scholar]
  21. Tulenko T. N. Regional sensitivity to vasoactive polypeptides in the human umbilicoplacental vasculature. Am J Obstet Gynecol. 1979 Nov 1;135(5):629–636. doi: 10.1016/s0002-9378(16)32988-x. [DOI] [PubMed] [Google Scholar]
  22. Wilkes B. M., Mento P. F. Bradykinin-induced vasoconstriction and thromboxane release in perfused human placenta. Am J Physiol. 1988 Jun;254(6 Pt 1):E681–E686. doi: 10.1152/ajpendo.1988.254.6.E681. [DOI] [PubMed] [Google Scholar]

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