title: Short-term suppression of the renin-angiotensin system in mice associated             with hypertension during pregnancy.
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.
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance, University                     of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ishimaru
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Misuzu
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Tanomu
authors.initials: T
authors.lastname: Matsukura
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kunita
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yagami
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy; D046110:Hypertension, Pregnancy-Induced / Q000209:etiology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000068557:Olmesartan Medoxomil; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D002216:Captopril