Endocrine

, Volume 18, Issue 3, pp 239–245

Angiotensin-(1–7) in normal and preeclamptic pregnancy

  • David C. Merrill
  • Michael Karoly
  • Kai Chen
  • Carlos M. Ferrario
  • K. Bridget Brosnihan
Article

Abstract

Angiotensin-(1–7) (Ang-[1–7]) is a bioactive component of the renin-angiotensin system, which has depressor, vasodilatory, and antihypertensive actions. In normal pregnancy, we questioned whether the known rise in plasma angiotensin II (Ang II) is counterbalanced by an increase in plasma Ang-(1–7) and whether Ang-(1–7) levels are decreased in preeclampsia and may thus be a factor involved in the development of hypertension. Nulliparous preeclamptic subjects, third-trimester normotensive pregnant subjects, and a nonpregnant group were enrolled (n=15/group). Preeclamptic subjects had no previous history of hypertension or renal, connective-tissue, or metabolic disease, but at the time of delivery had significant hypertension (159±3/98±3 mmHg) and ≥3+ proteinuria. Plasma Ang-(1–7) was increased by 51% in normal pregnancy (p<0.05). Plasma Ang I, Ang II, and renin activity were also significantly elevated in normal pregnancy. In preeclamptic subjects, Ang-(1–7) was significantly decreased (p<0.01) compared with normal pregnant subjects. All other components of the renin-angiotensin-aldosterone system, except serum angiotensin-converting enzyme, were reduced in preeclamptic subjects compared with normal pregnant subjects; only plasma Ang II remained elevated in preeclamptic compared with nonpregnant subjects. These studies demonstrate, for the first time, increased plasma Ang-(1–7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1–7) in preeclamptic subjects compared with normal pregnant subjects. In preeclampsia the decreased plasma Ang-(1–7) in the presence of elevated Ang II is consistent with the development of hypertension.

Key Words

Angiotensin peptides angiotensin-(1–7) angiotensin II pregnancy preeclampsia vasoactive peptides 

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References

  1. 1.
    The Working Group on High Blood Pressure in Pregnancy. National High Blood Pressure Education Program (NHPEP). (1991). Publication no. 91-3029. United States Department of Health and Human Services, Bethesda, MD.Google Scholar
  2. 2.
    August, P., Lenz, T., Ales, K. L., Druzin, M. L., Edersheim, T. G., Hutson, J. M., Muller, F. B., Laragh, J. H., and Sealey, J. E. (1990). Am. J. Obstet. Gynecol. 163, 1612–1621.PubMedGoogle Scholar
  3. 3.
    August, P. and Sealey, J. E. (1990). In: Hypertension pathophysiology, diagnosis, and management. Laragh, J. H. and Brenner, B. M. (eds.). Raven: New York.Google Scholar
  4. 4.
    Walsh, S. W. (1985). Am. J. Obstet. Gynecol. 152, 335–340.PubMedGoogle Scholar
  5. 5.
    Minuz, P., Covi, G., Paluani, F., Degan, M., Lechi, C., Corsato, M., and Lechi, A. (1988). Hypertension 11, 550–556.PubMedGoogle Scholar
  6. 6.
    Elebute, O. A. and Mills, I. H. (1976). In: Hypertension in pregnancy. Lindheimer, K. Z. (ed.). Wiley: New York.Google Scholar
  7. 7.
    Kyle, P. M., Campbell, S., Buckley, D., Kissane, J., de Swiet, M., Albano, J., Miller, J. G., and Redman, C. W. (1996). Br. J. Obstet. Gynaecol. 103, 981–987.PubMedGoogle Scholar
  8. 8.
    Millar, J. G., Campbell, S. K., Albano, J. D., Higgins, B. R., and Clark, A. D. (1996). Br. J. Obstet. Gynaecol. 103, 421–426.PubMedGoogle Scholar
  9. 9.
    Valdes, G., Corthorn, J., Oyarzun, E., Berrios, C., Foradori, A., Germain, A. M., and Villarroel, L. (1998). Prenat. Neonat. Med. 3, 474–481.Google Scholar
  10. 10.
    Odar-Cederlöf, I., Floberg, J., Theodorsson, E., and Fried, S. (1997). Hypertens. Pregnancy 16, 19–34.Google Scholar
  11. 11.
    Gant, N. F., Daley, G. L., Chand, S., Whalley, P. J., and MacDonald, P. C. (1973). J. Clin. Invest. 52, 2682–2689.PubMedCrossRefGoogle Scholar
  12. 12.
    Ferrario, C. M., Chappell, M. C., Tallant, E. A., Brosnihan, K. B., and Diz, D. (1997). Hypertension 30, 535–541.PubMedGoogle Scholar
  13. 13.
    Brosnihan, K. B., Li, P., and Ferrario, C. M. (1996). Hypertension 27, 523–528.PubMedGoogle Scholar
  14. 14.
    Porsti, I., Bara, A. T., Busse, R., and Hecker, M. (1994). Br. J. Pharmacol. 111, 652–654.PubMedGoogle Scholar
  15. 15.
    Osei, S. Y., Ahima, R. S., Minkes, R. K., Weaver, J. P., Khosla, M. C., and Kadowitz, P. J. (1993). Eur. J. Pharmacol. 234, 35–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Luque, M., Martin, P., Martell, N., Fernandez, C., Brosnihan, K. B., and Ferrario, C. M. (1996). J. Hypertens. 14, 99–805.CrossRefGoogle Scholar
  17. 17.
    Iyer, S. N., Ferrario, C. M., and Chappell, M. C. (1998). Hypertension 31, 356–361.PubMedGoogle Scholar
  18. 18.
    Campbell, D. J., Kladis, A., and Duncan, A. M. (1994). Hypertension 23, 439–449.PubMedGoogle Scholar
  19. 19.
    Kohara, K., Brosnihan, K. B., and Ferrario, C. M. (1993). Peptides 14, 883–891.PubMedCrossRefGoogle Scholar
  20. 20.
    Ferrario, C. M., Smith, R. D., Brosnihan, K. B., Chappell, M. C., Campese, V. M., Vesterqvist, O., Liao, W., Ruddy, M. C., and Grim, C. E. (2002). Am. J. Hypertens. 15, 557–564.PubMedCrossRefGoogle Scholar
  21. 21.
    Ferrario, C. M., Martell, N., Yunis, C., Flack, J. M., Chappell, M. C., Brosnihan, K. B., Dean, R. H., Fernandez, A., Novikov, S. V., Pinillas, C., and Luque, M. (1998). Am. J. Hypertens. 11, 137–146.PubMedCrossRefGoogle Scholar
  22. 22.
    Valdes, G., Germain, A. M., Corthorn, J., Berrios, C., Foradori, A. C., Ferrario, C. M., and Brosnihan, K. B. (2001). Endocrine 16, 117–122.PubMedCrossRefGoogle Scholar
  23. 23.
    Pipkin, F. B. and Baker, P. N. (1997). Hypertension 30, 1247–1252.Google Scholar
  24. 24.
    Carey, R. M., Wang, Z. Q., and Siragy, H. M. (2000). Hypertension 35(Suppl. 1, Pt. 2), 155–163.PubMedGoogle Scholar
  25. 25.
    Welches, W., Brosnihan, K. B., and Ferrario, C. M. (1993). Life Sci. 52, 1461–1480.PubMedCrossRefGoogle Scholar
  26. 26.
    Kohara, K., Tabachi, Y., Senanayake, P., Brosnihan, K. B., and Ferrario, C. M. (1991). Peptides 12, 1135–1141.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • David C. Merrill
    • 1
  • Michael Karoly
    • 1
  • Kai Chen
    • 1
  • Carlos M. Ferrario
    • 2
  • K. Bridget Brosnihan
    • 2
  1. 1.Department of Obstetrics and GynecologyWake Forest University School of MedicineWinston-Salem
  2. 2.Hypertension and Vascular Disease CenterWake Forest University School of Medicine, Medical Center BoulevardWinston-Salem

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