Open Access

Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy

  • Authors:
    • Tomohiro Ishimaru
    • Junji Ishida
    • Shoko Nakamura
    • Misuzu Hashimoto
    • Tanomu Matsukura
    • Ayumi Nakamura
    • Satoshi Kunita
    • Fumihiro Sugiyama
    • Ken-Ichi Yagami
    • Akiyoshi Fukamizu
  • View Affiliations

  • Published online on: April 23, 2012     https://doi.org/10.3892/mmr.2012.886
  • Pages: 28-32
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Abstract

Pregnancy-induced hypertension or pre-eclampsia is a major disorder that may result in serious complications for the mother and fetus. It is characterized from maternal hypertension in late pregnancy and peripheral tissue damage, including kidney, heart and placenta, and the fetus suffers from intrauterine growth retardation (IUGR) and high perinatal mortality. Recently, it has been postulated that angiotensin II (Ang II), a potent vasoconstrictor in the renin-angiotensin system (RAS), plays a pivotal role in the pathogenesis of pre‑eclampsia; however, the beneficial effect of the suppression of RAS has not yet been fully elucidated. Previously, we generated a transgenic mouse model that developed pregnancy-associated hypertension (PAH) by the overproduction of Ang II in maternal circulation during late pregnancy. In addition, mice with PAH exhibited maternal and fetal abnormalities, such as proteinuria, cardiac hypertrophy, placental morphological changes and IUGR. In this study, in order to attenuate the activity of redundant RAS during the advanced stages of PAH, we administered olmesartan (Olm), an angiotensin receptor blocker, and captopril (Cp), an angiotensin converting enzyme inhibitor, from E17 to E19 days of gestation, and evaluated its effect on cardiac and placental abnormalities and fetal growth. Olm and Cp administration significantly lowered the blood pressure of mice with PAH, and placental histological change and severe IUGR were markedly ameliorated in both groups. On the contrary, Olm or Cp treatment had little effect on cardiac remodeling during the advanced stages of PAH. These findings highlight a variety of therapeutic actions of RAS repression on the progressive pathology of PAH in mice.

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July 2012
Volume 6 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Ishimaru, T., Ishida, J., Nakamura, S., Hashimoto, M., Matsukura, T., Nakamura, A. ... Fukamizu, A. (2012). Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy. Molecular Medicine Reports, 6, 28-32. https://doi.org/10.3892/mmr.2012.886
MLA
Ishimaru, T., Ishida, J., Nakamura, S., Hashimoto, M., Matsukura, T., Nakamura, A., Kunita, S., Sugiyama, F., Yagami, K., Fukamizu, A."Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy". Molecular Medicine Reports 6.1 (2012): 28-32.
Chicago
Ishimaru, T., Ishida, J., Nakamura, S., Hashimoto, M., Matsukura, T., Nakamura, A., Kunita, S., Sugiyama, F., Yagami, K., Fukamizu, A."Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy". Molecular Medicine Reports 6, no. 1 (2012): 28-32. https://doi.org/10.3892/mmr.2012.886